Neurogliovascular dysfunction in a model of repeated traumatic brain injury
Open accessAbstract
Traumatic brain injury (TBI) research has focused on moderate to severe injuries as their outcomes are significantly worse than those of a mild TBI (mTBI).However, recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders.Neuropathological studies of repeated TBI have identified changes in neuronal ionic concentrations, axonal injury, and cytoskeletal damage as important determinants of later life neurological and mood compromise; yet, there is a paucity of data on the contribution of neurogliovascular dysfunction to the progression of repeated TBI and alterations of brain function in the intervening period.Methods: Here, we established a mouse model of repeated TBI induced via three electromagnetically actuated impacts delivered to the intact skull at three-day intervals and determined the long-term deficits in neurogliovascular functioning in Thy1-ChR2 mice.Two weeks post the third impact, cerebral blood flow and cerebrovascular reactivity were measured with arterial spin labelling magnetic resonance imaging.Neuronal function was investigated through bilateral intracranial electrophysiological responses to optogenetic photostimulation.Vascular density of the site of impacts was measured with in vivo two photon fluorescence microscopy.Pathological analysis of neuronal survival and astrogliosis was performed via NeuN and GFAP immunofluorescence.Results: Cerebral blood flow and cerebrovascular reactivity were decreased by 50±16% and 70±20%, respectively, in the TBI cohort relative to sham-treated animals.Concomitantly, electrophysiological recordings revealed a 97±1% attenuation in peri-contusional neuronal reactivity relative to sham.Peri-contusional vascular volume was increased by 33±2% relative to sham-treated mice.Pathological analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes in neuronal survival.Conclusion: This work provides the first in-situ characterization of the long-term deficits of the neurogliovascular unit following repeated TBI.The findings will help guide the development of diagnostic markers as well as therapeutics targeting neurogliovascular dysfunction.
AI snapshot
Written from the paper’s full text.
TL;DR
Repeated mild closed-head impacts in Thy1-ChR2 mice produced persistent peri-contusional and some bilateral neurogliovascular dysfunction two weeks after the third impact, including reduced CBF/CVR, prolonged ATT, reduced optogenetic-evoked neuronal responses, increased vascular volume, and astrogliosis without neuronal loss. The authors conclude that serial individually mild impacts can cause pathology comparable to moderate TBI.
Key findings
- Peri-contusional resting CBF was 140±30 vs. 280±30 mL/min/100 mL in sham (p=0.001), and ATT was 260±50 vs. 120±6 ms (p=0.01); contralateral CBF and ATT were not significantly different.
- CVR to 10% CO2 was reduced peri-contusionally (50±10% vs. 250±30%, p=0.003) and contralaterally (45±7% vs. 250±40%, p=0.02).
- Evoked neuronal response amplitude to optogenetic photostimulation was reduced peri-contusionally (0.02±0.01 mV vs. 0.7±0.2 mV, p=0.02) and contralaterally (0.2±0.1 mV vs. 0.6±0.1 mV, p=0.04).
- Peri-contusional vascular volume increased (3.2±0.4% vs. 2.4±0.6%, p=0.02) and GFAP immunoreactivity increased (29±1% vs. 1.5±0.2%, p=0.009), with no significant changes in NeuN, MAP2, or neurofilament.
Methods
- Thirty-six 9-week-old Thy1-ChR2 mice underwent repeated CHI (n=19; 10 male, 9 female) or sham preparation (n=17; 9 male, 8 female); repeated TBI used three electromagnetically actuated impacts at 3-day intervals to the intact skull over S1FL (2 m/s, 1000 μm depth, 200 ms dwell, 1.5 mm tip).
- Two weeks after the third impact, mice underwent pCASL MRI for resting CBF, ATT, and CVR to 10% CO2; bilateral electrophysiology with 450 nm optogenetic photostimulation; in vivo two-photon fluorescence microscopy for vascular occupancy; and histopathology for NeuN, GFAP, MAP2, and neurofilament.
- Analysis used a logistic regression classifier to identify peri-contusional voxels, then linear mixed effects models or Kruskal-Wallis tests depending on normality and variance, with subject as a random effect for imaging.
Limitations
- Stated: cohort sizes precluded analysis of sex effects, and future larger cohorts are required; future work is also needed for 3D cerebrovascular segmentation, and rodent and human ages should not be conflated.
- Evident: final assay cohorts were small (MRI n=5–6, two-photon n=4, electrophysiology n=4), limiting power and subgroup analyses; assessments were at a single chronic time point two weeks after the final impact, so temporal progression is not captured; no behavioral outcomes are reported.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 73 cited sources checked · 0 supported · 0 flagged
- Findingown data
In mice with repeated traumatic brain injury, GFAP immunoreactivity in the peri-contusional cortex is increased compared to sham-treated mice.
“Increased peri-contusional vascular density was accompanied by an increase in GFAP immunoreactivity (29±1% for TBI mice, 1.5±0.2% for sham-treated mice, p = 0.009)”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, cerebrovascular reactivity to CO2 in impacted tissue is reduced compared to sham-treated mice.
“In TBI mice (n=6), the CO2-induced change in CBF of impacted tissue was 50±10%, compared to 250±30% in that of sham-treated mice (n=5) (χ2= 9.0, p=0.003)”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, cerebral blood flow in the contralateral hemisphere is not reduced relative to sham-treated mice.
“CBF of the contralateral hemisphere (240±20 mL/min/100 mL, n=5) was not reduced relative to that of sham-treated mice (210±20 mL/min/100 mL, n=5, χ2= 2.75, p=0.1)”
Quote in the paperNot a substantial claim - Findingown data
T2-weighted anatomical images acquired 24 h after a single CHI in a subset of mice confirmed an absence of significant structural damage following a single insult.
“T2-weighted anatomical images of the site of the impact acquired at 24 h after a single CHI in a subset of mice confirmed an absence of significant structural damage following a single insult (Figure 1)”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, there is no significant change in neuronal survival in the peri-contusional cortex compared to sham-treated mice.
“Pathological analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes in neuronal survival.”
- Also stated in: § Introduction · plain
“despite no significant changes in neuronal density on NeuN, neurofilament, and MAP2 immunofluorescence.”
Quote in the paperNot a substantial claim - Also stated in: § Introduction · plain
- Findingown data
Two weeks following the final impact, T2-weighted anatomical imaging revealed hypointense regions at the site of the impacts.
“two weeks following the final impact the same anatomical imaging revealed hypointense regions at the site of the impacts”
Quote in the paperSubstantial claim - Findingown data
In vivo two-photon fluorescence microscopy indicated increased peri-contusional vascular volume.
“In vivo two-photon fluorescence microscopy indicated increased peri-contusional vascular volume.”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, the evoked response amplitude in the contralateral hemisphere is reduced compared to sham-treated mice.
“the evoked response amplitude of contralateral hemisphere (0.2±0.1 mV) was reduced by 67±19% relative to that of sham-treated mice (0.6±0.1 mV, χ2=4.08, p=0.04).”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, resting cerebral blood flow in the peri-contusional cortex is reduced compared to sham-treated mice.
“TBI mice (n=5) showed reduced perfusion of peri-contusional cortex (140±30 mL/min/100 mL) relative to perfusion level in the corresponding brain region of sham-treated mice (280±30 mL/min/100 mL, n=5, χ2= 10.78, p=0.001)”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, vascular density in the peri-contusional cortex is increased compared to sham-treated mice.
“the TBI mice showed increased vascular density on in vivo 2-photon fluorescence microscopy in the cortical region surrounding the impacts' site relative to that in the homologous region in sham mice (3.2±0.4% TBI, 2.4±0.6% sham, p=0.02, Figure 6).”
- Also stated in: § Abstract · plain
“Peri-contusional vascular volume was increased by 33±2% relative to sham-treated mice.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingnone given
Sham-treated animals showed no contrast on T2-weighted imaging.
“Sham-treated animals showed no contrast on T2-weighted imaging.”
Quote in the paperNot a substantial claim - Findingown data
In mice with repeated traumatic brain injury, the amplitude of evoked neuronal responses to photostimulation in peri-contusional tissue is reduced compared to sham-treated mice.
“The amplitude of evoked neuronal responses to photostimulation of peri-contusional tissue of TBI mice (n=4) was reduced relative to that of sham-treated mice (n=4) (0.02±0.01 mV TBI vs. 0.7±0.2 mV sham-treated, χ2= 5.33, p=0.02).”
- Also stated in: § Abstract · plain
“electrophysiological recordings revealed a 97±1% attenuation in peri-contusional neuronal reactivity relative to sham.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In mice with repeated traumatic brain injury, the proportion of GFAP-positive cells contralaterally to the injured site is approximately normal compared to sham-treated mice.
“an approximately normal proportion of GFAP-positive cells were present contralaterally to the injured site (4±2% for TBI vs. 1.7±0.5% for sham-treated mice, p=0.17).”
Quote in the paperNot a substantial claim - Findingown data
In mice with repeated traumatic brain injury, arterial transit time in the peri-contusional cortex is longer than in sham-treated mice.
“ATT of TBI mice was longer, on average, than that of sham-treated mice (260±50 ms in TBI vs. 120±6 ms in sham treated mice, χ2= 6.53, p=0.01).”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, arterial transit time in the contralateral hemisphere is not reduced relative to sham-treated mice.
“nor was the ATT of the contralateral hemisphere reduced relative to that of sham-treated mice (108±20 ms in TBI vs. 150±20 ms in sham-treated mice, χ2= 3.33, p=0.07).”
Quote in the paperNot a substantial claim - Findingown data
Neuronal density of TBI animals was not different from that of sham-treated mice in either pericontusional or contralateral cortex.
“The neuronal density of TBI animals was not different from that of sham-treated mice in either region.”
Quote in the paperSubstantial claim - Findingown data
In mice with repeated traumatic brain injury, contralateral cerebrovascular reactivity is reduced compared to sham-treated mice.
“TBI mice had reduced contralateral CVR compared to sham-treated mice (45±7% TBI vs. 250±40% sham, χ2= 5.33, p=0.02).”
Quote in the paperSubstantial claim - Findingown data
No significant changes in NeuN, MAP2, or neurofilament immunofluorescence were observed in the perilesional cortex of TBI mice compared with sham-treated mice.
“We observed no significant changes in NeuN, MAP2, or neurofilament immunofluorescence in the perilesional cortex (NeuN: 16±2% for TBI vs. 20.4±0.4% for sham-treated mice, p = 0.11; MAP2: 77±9% for TBI vs. 58±2% for sham-treated mice, p = 0.08; and neurofilament: 77±33% for TBI mice vs. 58±23% for sham-treated mice, p = 0.1).”
Quote in the paperSubstantial claim - Findingown data
We observed an increase in GFAP fluorescence.
“we observed an increase in GFAP fluorescence.”
Quote in the paperSubstantial claim - Findingown data
Neuronal dysfunction was manifested as bilaterally reduced amplitude of evoked responses to photoactivation of channelrhodopsin.
“Neuronal dysfunction was manifested as bilaterally reduced amplitude of evoked responses to photoactivation of channelrhodopsin.”
Quote in the paperSubstantial claim - Findingreasoning
When challenged with an increase of CO2 in the inspired gas mixture, repeated TBI mice exhibited depressed cerebral blood flow response relative to sham-operated mice.
“When challenged with an increase of CO2 in the inspired gas mixture, repeated TBI mice exhibited depressed cerebral blood flow response relative to sham-operated mice.”
Quote in the paperSubstantial claim - Findingown data
In vivo two-photon fluorescence microscopy in our study indicated increased vessel density near the site of the injury in repeated TBI-treated mice relative to shams.
“In vivo two-photon fluorescence microscopy in our study indeed indicated increased vessel density near the site of the injury in repeated TBI-treated mice relative to shams”
Quote in the paperSubstantial claim - Findingown data
Mice that underwent repeated TBI had longer arterial transit time in damaged tissue relative to sham-treated mice.
“Mice that underwent repeated TBI had longer arterial transit time in damaged tissue relative to sham-treated mice.”
Quote in the paperSubstantial claim - Premisecitation
Cerebrovascular reactivity is compromised following moderate to severe traumatic brain injury.
“cerebrovascular reactivity (CVR), the brain's ability to elevate blood flow above baseline, is compromised following moderate to severe TBI 9”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Amyot F Kenney K Moore C Harber M Turtzo LC Shenouda CN Imaging of cerebrovascular function in chronic traumatic brain injury J Neurotrauma 2017 5 10 1116 1123 PMC6016094 29065769
Not checked in the free run.
- Premisecitation
Repeated mild traumatic brain injury in preclinical models results in compromised blood-brain-barrier.
“their histopathological characterization indicated that mild TBI, when repeated, results in compromised blood-brain-barrier, pyramidal neuron death, astrocytic activation, and recruitment of macrophages/ microglia to the site of the injury 11-15.”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [11] Mouzon BC Bachmeier C Ferro A Ojo J-O Crynen G Acker CM Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model Ann Neurol 2014 75 241 254 24243523
Not checked in the free run.
- cites [12] Tzekov R Quezada A Gautier M Biggins D Frances C Mouzon B Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model J Neuropathol Exp Neurol 2014 73 345 361 24607965
Not checked in the free run.
- cites [13] Yang Z Wang P Morgan D Lin D Pan J Lin F Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model Sci Rep 2015 5 11178 26058556 PMC4461921
Not checked in the free run.
- cites [14] Laurer HL Bareyre FM Lee VM Trojanowski JQ Longhi L Hoover R Mild head injury increasing the brain's vulnerability to a second concussive impact J Neurosurg 2001 95 859 870 11702878
Not checked in the free run.
- cites [15] Ojo J-O Mouzon B Greenberg MB Bachmeier C Mullan M Crawford F Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice J Neuropathol Exp Neurol 2013 72 137 151 23334597
Not checked in the free run.
- Premisecitation
Repeated mild traumatic brain injury is associated with an increased risk of late-onset neurodegenerative and mood disorders.
“recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders.”
- Also stated in: § Introduction · hedged
“there is mounting evidence of an association between mTBI and late-onset neurodegenerative and mood disorders 2-4.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [2] Bryant R Post-traumatic stress disorder vs traumatic brain injury Dialogues Clin Neurosci 2011 13 251 262 22034252 PMC3182010
Not checked in the free run.
- cites [3] Van Den Heuvel C Thornton E Vink R Traumatic brain injury and Alzheimer's disease: a review Prog Brain Res 2007 161 303 316 17618986
Not checked in the free run.
- cites [4] Lee Y-K Hou S-W Lee C-C Hsu C-Y Huang Y-S Su Y-C Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study PLoS One 2013 8 e62422 23658727 PMC3641064
Not checked in the free run.
- Also stated in: § Introduction · hedged
- Premisecitation
Cerebrovascular reactivity is critical in the ensuing pathological progression and functional decline after traumatic brain injury.
“has been identified as critical in the ensuing pathological progression and functional decline 10”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] Kenney K Amyot F Haber M Pronger A Bogoslovsky T Moore C Cerebral vascular injury in traumatic brain injury Exp Neurol 2016 275 Pt 3: 353-366 26048614
Not checked in the free run.
- Premisecitation
Functional assessments of the neurogliovascular unit following repeated mild traumatic brain injury are lacking.
“Despite the progress made in characterizing repeated mild TBI using histopathology and behavioural testing, functional assessments of the neurogliovascular unit following repeated mTBI are lacking 17.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Fehily B Fitzgerald M Repeated mild traumatic brain injury: potential mechanisms of damage Cell Transplant 2017 26 1131 1155 28933213 PMC5657727
Not checked in the free run.
- Premisecitation
Repeated mild traumatic brain injury in preclinical models results in pyramidal neuron death.
“their histopathological characterization indicated that mild TBI, when repeated, results in compromised blood-brain-barrier, pyramidal neuron death, astrocytic activation, and recruitment of macrophages/ microglia to the site of the injury 11-15.”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [11] Mouzon BC Bachmeier C Ferro A Ojo J-O Crynen G Acker CM Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model Ann Neurol 2014 75 241 254 24243523
Not checked in the free run.
- cites [12] Tzekov R Quezada A Gautier M Biggins D Frances C Mouzon B Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model J Neuropathol Exp Neurol 2014 73 345 361 24607965
Not checked in the free run.
- cites [13] Yang Z Wang P Morgan D Lin D Pan J Lin F Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model Sci Rep 2015 5 11178 26058556 PMC4461921
Not checked in the free run.
- cites [14] Laurer HL Bareyre FM Lee VM Trojanowski JQ Longhi L Hoover R Mild head injury increasing the brain's vulnerability to a second concussive impact J Neurosurg 2001 95 859 870 11702878
Not checked in the free run.
- cites [15] Ojo J-O Mouzon B Greenberg MB Bachmeier C Mullan M Crawford F Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice J Neuropathol Exp Neurol 2013 72 137 151 23334597
Not checked in the free run.
- Premisecitation
Repeated mild traumatic brain injury in preclinical models results in astrocytic activation.
“their histopathological characterization indicated that mild TBI, when repeated, results in compromised blood-brain-barrier, pyramidal neuron death, astrocytic activation, and recruitment of macrophages/ microglia to the site of the injury 11-15.”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [11] Mouzon BC Bachmeier C Ferro A Ojo J-O Crynen G Acker CM Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model Ann Neurol 2014 75 241 254 24243523
Not checked in the free run.
- cites [12] Tzekov R Quezada A Gautier M Biggins D Frances C Mouzon B Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model J Neuropathol Exp Neurol 2014 73 345 361 24607965
Not checked in the free run.
- cites [13] Yang Z Wang P Morgan D Lin D Pan J Lin F Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model Sci Rep 2015 5 11178 26058556 PMC4461921
Not checked in the free run.
- cites [14] Laurer HL Bareyre FM Lee VM Trojanowski JQ Longhi L Hoover R Mild head injury increasing the brain's vulnerability to a second concussive impact J Neurosurg 2001 95 859 870 11702878
Not checked in the free run.
- cites [15] Ojo J-O Mouzon B Greenberg MB Bachmeier C Mullan M Crawford F Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice J Neuropathol Exp Neurol 2013 72 137 151 23334597
Not checked in the free run.
- Study design and conductnone given
The model was optimized to potentiate clinical relevance by limiting the amount of injury induced by each individual closed head injury, rendering individual impacts mild (single impact being negative on neuroimaging).
“The model was optimized so as to potentiate clinical relevance by limiting the amount of injury induced by each individual closed head injury, i.e., by rendering the individual impacts mild (single impact being negative on neuroimaging).”
Quote in the paperSubstantial claim - Interpretationown data
This study provides the first in situ functional assessments of neuronal and cerebrovascular functions in the chronic phase of a series of mild impacts.
“In this study, we report on the first in situ functional assessments of the neuronal and cerebrovascular functions in the chronic phase of a series of mild impacts.”
- Also stated in: § Abstract · plain
“This work provides the first in-situ characterization of the long-term deficits of the neurogliovascular unit following repeated TBI.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Premisecitation
Alterations of cerebral blood flow resulting from experimental repeated TBI are poorly understood, as investigations have been limited by modalities that lack topographical information.
“Alterations of cerebral blood flow resulting from experimental repeated TBI are poorly understood, as investigations have been limited by modalities that lack topographical information 39.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [39] Hylin MJ Orsi SA Rozas NS Hill JL Zhao J Redell JB Repeated mild closed head injury impairs short-term visuospatial memory and complex learning J Neurotrauma 2013 30 716 726 23489238
Not checked in the free run.
- Interpretationnone given
This study provides the first in vivo measures of neurovascular functioning in chronic repeated TBI, induced via serial closed head injuries.
“This study provides the first in vivo measures of neurovascular functioning in chronic repeated TBI, induced via serial closed head injuries.”
Quote in the paperSubstantial claim - Interpretationown data
Individual mild insults delivered in series appear similar to a single moderate brain injury on neuroimaging.
“suggesting that individual mild insults delivered in series appear similar to a single moderate brain injury on neuroimaging.”
Quote in the paperSubstantial claim - Interpretationown data
The observed cerebrovascular findings indicate impairment of the brain's ability to maintain circulation to peri-contusional tissue.
“These findings are indicative of impairment of the brain's ability to maintain circulation to peri-contusional tissue.”
Quote in the paperSubstantial claim - Interpretationcitation
T2 hypointensities suggest microhemorrhages.
“T2 hypointensities suggest microhemorrhages.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [37] Donovan V Bianchi A Hartman R Bhanu B Carson MJ Obenaus A Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury Neuroimage Clin 2012 1 18 28 24179733 PMC3757717
Not checked in the free run.
- cites [38] Wu G Xi G Hua Y Sagher O T2* magnetic resonance imaging sequences reflect brain tissue iron deposition following intracerebral hemorrhage Transl Stroke Res 2010 1 31 34 20811505 PMC2930789
Not checked in the free run.
- Interpretationcitation
Reduced cerebral blood flow may be the result of biomechanical damage to vessels caused by the initial impact.
“Reduced cerebral blood flow may be the result of biomechanical damage to vessels caused by the initial impact 40.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] Meaney DF Smith DH Biomechanics of concussion Clin Sports Med 2011 30 19 31 21074079 PMC3979340
Not checked in the free run.
- Premisecitation
The 3-day inter-impact interval was motivated by prior reports of a "window of vulnerability," whereby greatest behavioural deficits are seen in mice impacted every 3 days.
“The 3-day inter-impact interval was motivated by prior reports of a “window of vulnerability,” whereby greatest behavioural deficits are seen in mice impacted every 3 days 34.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Longhi L Saatman KE Fujimoto S Raghupathi R Meaney DF Davis J Temporal window of vulnerability to repetitive experimental concussive brain injury Neurosurgery 2005 56 364 74 discussion 364-74 15670384
Not checked in the free run.
- Premisecitation
Behavioural assessments of repeated mild traumatic brain injury mice reveal cognitive and motor deficits greater than those predicted from summation of compromise seen in mice challenged with a single mild traumatic brain injury.
“behavioural assessments of repeated mTBI mice have revealed cognitive and motor deficits greater than those predicted from summation of compromise seen in mice challenged with a single mild TBI 16.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] Mouzon B Chaytow H Crynen G Bachmeier C Stewart J Mullan M Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes J Neurotrauma 2012 29 2761 2773 22900595 PMC13588329
Not checked in the free run.
- Premisecitation
At least three days is typically required for military servicemen to return to duty following an mTBI.
“at least three days is typically required for military servicemen to return to duty following an mTBI 7.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] DoD Policy Guidance for Management of Mild Traumatic Brain Injury. 28 September 2012 https://www.hsdl.org/?view&did=722999
Not checked in the free run.
- Study design and conductown data
The sizes of cohorts in the present study precluded analysis of the sex effects.
“the sizes of cohorts precluded analysis of the sex effects”
Quote in the paperNot a substantial claim - Premisecitation
Repeated mild traumatic brain injury in preclinical models results in recruitment of macrophages/microglia to the site of injury.
“their histopathological characterization indicated that mild TBI, when repeated, results in compromised blood-brain-barrier, pyramidal neuron death, astrocytic activation, and recruitment of macrophages/ microglia to the site of the injury 11-15.”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [11] Mouzon BC Bachmeier C Ferro A Ojo J-O Crynen G Acker CM Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model Ann Neurol 2014 75 241 254 24243523
Not checked in the free run.
- cites [12] Tzekov R Quezada A Gautier M Biggins D Frances C Mouzon B Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model J Neuropathol Exp Neurol 2014 73 345 361 24607965
Not checked in the free run.
- cites [13] Yang Z Wang P Morgan D Lin D Pan J Lin F Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model Sci Rep 2015 5 11178 26058556 PMC4461921
Not checked in the free run.
- cites [14] Laurer HL Bareyre FM Lee VM Trojanowski JQ Longhi L Hoover R Mild head injury increasing the brain's vulnerability to a second concussive impact J Neurosurg 2001 95 859 870 11702878
Not checked in the free run.
- cites [15] Ojo J-O Mouzon B Greenberg MB Bachmeier C Mullan M Crawford F Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice J Neuropathol Exp Neurol 2013 72 137 151 23334597
Not checked in the free run.
- Interpretationcitation
Cortical swelling and the ensuing elevation in intracranial pressure may also have contributed to reduced resting cerebral blood flow.
“Cortical swelling and the ensuing elevation in intracranial pressure may also have contributed to reduced resting cerebral blood flow 41.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [41] Unterberg AW Stover J Kress B Kiening KL Edema and brain trauma Neuroscience 2004 129 1021 1029 15561417
Not checked in the free run.
- Premisecitation
Previous work on repeated controlled cortical impacts in rats reported extravascular iron deposition near lesions composed of blood.
“previous work on repeated controlled cortical impacts (two impacts delivered to opposite hemispheres at 3 and 7 day inter-impact-intervals) in rats reported extravascular iron deposition near lesions composed of blood 37.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] Donovan V Bianchi A Hartman R Bhanu B Carson MJ Obenaus A Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury Neuroimage Clin 2012 1 18 28 24179733 PMC3757717
Not checked in the free run.
- Interpretationcitation
The observed lengthening of arterial transit time could manifest increased dispersion of microvascular route lengths and microvascular reactivity, which have been previously reported in models of moderate TBI.
“The observed lengthening of arterial transit time could manifest, as a result, increased dispersion of microvascular route lengths and microvascular reactivity, which have been previously reported in models of moderate TBI 44,45.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [44] Hayward NMEA Tuunanen PI Immonen R Ndode-Ekane XE Pitkänen A Gröhn O Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats J Cereb Blood Flow Metab 2011 31 166 177 20485295 PMC3049481
Not checked in the free run.
- cites [45] Østergaard L Engedal TS Aamand R Mikkelsen R Iversen NK Anzabi M Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury J Cereb Blood Flow Metab 2014 34 1585 1598 25052556 PMC4269727
Not checked in the free run.
- Interpretationreasoning
Chronically depressed cerebrovascular reactivity has the potential to worsen functional outcomes.
“Chronically depressed cerebrovascular reactivity has the potential to worsen functional outcomes.”
Quote in the paperSubstantial claim - Premisecitation
Pharmacological impairment of the coupling between neuronal activity and CBF in mice has been shown to result in cognitive impairments.
“Pharmacological impairment of the coupling between neuronal activity and CBF in mice has been shown to result in cognitive impairments 51.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] Tarantini S Hertelendy P Tucsek Z Valcarcel-Ares MN Smith N Menyhart A Pharmacologically-induced neurovascular uncoupling is associated with cognitive impairment in mice J Cereb Blood Flow Metab 2015 35 1871 1881 26174328 PMC4635246
Not checked in the free run.
- Premisecitation
When short on glucose, astrocytes are unable to provide adequate support to neurons, further endangering neuronal survival.
“When short on glucose, the astrocytes are unable to provide adequate support to neurons, further endangering neuronal survival 55.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [55] Lee C-Y Dallérac G Ezan P Anderova M Rouach N Glucose tightly controls morphological and functional properties of astrocytes Front Aging Neurosci 2016 8 82 27148048 PMC4834307
Not checked in the free run.
- Interpretationreasoning
The observed deficits in cerebrovascular reactivity to hypercapnia likely resulted from incomplete pruning of new vessels in combination with mechanical damage to the existing vessels.
“The observed deficits in cerebrovascular reactivity to hypercapnia likely resulted from incomplete pruning of new vessels in combination with mechanical damage to the existing vessels.”
Quote in the paperSubstantial claim - Interpretationown data
The reduced contractility of immature new vessels may have contributed to increases in heterogeneity of vascular transit times.
“the reduced contractility of immature new vessels may have contributed to increases in heterogeneity of vascular transit times 42.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Carmeliet P Angiogenesis in health and disease Nat Med 2003 9 653 660 12778163
Not checked in the free run.
- Interpretationown data
A series of individually mild impacts can trigger pathological changes on par with those seen post moderate TBI.
“Our findings indicate that a series of individually mild impacts can trigger pathological changes on par with those seen post moderate TBI”
Quote in the paperSubstantial claim - Interpretationreasoning
This is the first report of cerebrovascular remodeling and arterial transit time elongation in a model of repeated TBI.
“this is the first report of cerebrovascular remodeling and arterial transit time elongation in a model of repeated TBI.”
Quote in the paperSubstantial claim - Interpretationown data
This study provides initial characterization of neurogliovascular dysfunction two weeks following repeated TBI.
“In conclusion, this study provides initial characterization of neurogliovascular dysfunction two weeks following repeated TBI.”
Quote in the paperSubstantial claim - Premisecitation
Electrophysiological responses of cortical pyramidal neurons of Thy1-ChR2 mice to photostimulation have been shown to be comparable to those evoked by peripheral functional stimulation, such as forelimb stimulation.
“Electrophysiological responses of cortical pyramidal neurons of Thy1-ChR2 mice to photostimulation have been shown to be comparable to those evoked by peripheral functional stimulation, such as forelimb stimulation 57.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [57] Vazquez AL Fukuda M Crowley JC Kim S-G Neural and hemodynamic responses elicited by forelimb- and photo-stimulation in channelrhodopsin-2 mice: insights into the hemodynamic point spread function Cereb Cortex 2014 24 2908 2919 23761666 PMC4193461
Not checked in the free run.
- Interpretationreasoning
Focal damage at the site of the injury may well have affected the contralateral hemisphere, given the density of transcallosal connections between homologous regions of the cortex.
“Given the density of transcallosal connections between homologous regions of the cortex, focal damage at the site of the injury may well have affected the contralateral hemisphere.”
Quote in the paperNot a substantial claim- Rests on an assumption: Transcallosal connections between homologous regions of the cortex are dense.
- Interpretationown data
We present the first measures of impaired neuronal excitability (in response to opsin photoactivation) not only peri-contusionally, but also contralaterally, two weeks following repeated TBI.
“Furthermore, we present the first measures of impaired neuronal excitability (in response to opsin photoactivation) not only peri-contusionally, but also contralaterally, two weeks following repeated TBI.”
Quote in the paperSubstantial claim
- May combine two claims. 22
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 17
May combine two claims.
Findingown dataTwo weeks post final impact, resting cerebral blood flow was reduced at the site of the impacts, but not contralaterally or in sham-treated animals.
“Two weeks post final impact, we observed a reduction of resting cerebral blood flow at the site of the impacts that was not present either contralaterally or in sham-treated animals.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataNo differences in NeuN, MAP2, or neurofilament immunofluorescence were observed in the contralateral cortex of TBI mice compared with sham-treated mice.
“No differences were observed in the contralateral cortex either (NeuN: 22±1% for TBI vs. 19±1% for sham-treated mice, p = 0.1; MAP2: 63±7% for TBI vs. 46±3% for sham-treated mice, p = 0.2; and neurofilament: 25±3% for TBI vs. 28±2% for sham-treated mice, p = 0.8).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataThe average lesion volume in the repeated traumatic brain injury cohort estimated from NeuN staining was 100 ± 10 μm3.
“The average lesion volume in the TBI cohort estimated from NeuN staining was 100 ± 10 μm3.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe observed increases in cerebrovascular density and GFAP immunoreactivity were limited to the peri-contusional cortex, while impairments of cerebrovascular and neuronal reactivity were observed bilaterally, although peri-contusional effects were much stronger than contralateral ones.
“While the observed increases in cerebrovascular density and GFAP immunoreactivity were limited to the peri-contusional cortex, impairments of cerebrovascular and neuronal reactivity were observed bilaterally, although the peri-contusional effects were much stronger than the contralateral ones.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationRepeated head trauma amplifies the risk of chronic traumatic encephalopathy and neuropsychiatric conditions including depression and suicidal tendencies.
“This risk is amplified in the case of repeated head trauma, which may lead to chronic traumatic encephalopathy—a progressive neurodegenerative disease involving cognitive decline—as well as neuropsychiatric conditions including depression and suicidal tendencies 5,6.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [5] McKee AC Cantu RC Nowinski CJ Hedley-Whyte ET Gavett BE Budson AE Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury J Neuropathol Exp Neurol 2009 68 709 735 19535999 PMC2945234
Not checked in the free run.
- cites [6] McKee AC Stern RA Nowinski CJ Stein TD Alvarez VE Daneshvar DH The spectrum of disease in chronic traumatic encephalopathy Brain 2013 136 43 64 23208308 PMC3624697
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRodent and human ages should not be conflated due to different time scales of important complex biological processes.
“rodent and human ages should not be conflated due to the different time scales of important complex biological processes 18,29.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [18] Agoston DV How to translate time? The temporal aspect of human and rodent biology Front Neurol 2017 8 92 28367138 PMC5355425
Not checked in the free run.
- cites [29] Scopaz KA Hatzenbuehler JR Risk modifiers for concussion and prolonged recovery Sports Health 2013 5 537 541 24427429 PMC3806172
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChronically reduced resting cerebral blood flow may lead to irreversible selective neuronal loss.
“Chronically reduced resting CBF may lead to irreversible selective neuronal loss 28.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Baron J-C Yamauchi H Fujioka M Endres M Selective neuronal loss in ischemic stroke and cerebrovascular disease J Cereb Blood Flow Metab 2014 34 2 18 24192635 PMC3887360
Not checked in the free run.
May combine two claims.
PremisecitationSimilar "windows of vulnerability" have been observed in the clinic; in the most extreme cases, a second impact can be fatal.
“Similar “windows of vulnerability” have been observed in the clinic as well: in the most extreme cases, a second impact can be fatal 35.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Bey T Ostick B Second impact syndrome West J Emerg Med 2009 10 6 10 19561758 PMC2672291
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn the human population, young adults suffer a disproportionate number of mild head injuries through participation in athletics and military service.
“in the human population, young adults suffer a disproportionate number of mild head injuries through participation in athletics and military service 18,29.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [18] Agoston DV How to translate time? The temporal aspect of human and rodent biology Front Neurol 2017 8 92 28367138 PMC5355425
Not checked in the free run.
- cites [29] Scopaz KA Hatzenbuehler JR Risk modifiers for concussion and prolonged recovery Sports Health 2013 5 537 541 24427429 PMC3806172
Not checked in the free run.
May combine two claims.
InterpretationcitationAn increase of cerebral blood volume concomitant to decreased cerebral blood flow may have produced a decrease of blood velocity and a decreased efficiency of metabolite delivery by the circulation, as seen in moderate to severe TBI.
“An increase of cerebral blood volume concomitant to decreased cerebral blood flow may have produced a decrease of blood velocity and a decreased efficiency of metabolite delivery by the circulation, as seen in moderate to severe TBI 40,43.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [40] Meaney DF Smith DH Biomechanics of concussion Clin Sports Med 2011 30 19 31 21074079 PMC3979340
Not checked in the free run.
- cites [43] Giza CC Hovda DA The new neurometabolic cascade of concussion Neurosurgery 2014 75 Suppl 4 S24 33 25232881 PMC4479139
Not checked in the free run.
May combine two claims.
InterpretationcitationIncreased peri-contusional vascular volume may have resulted either from angiogenesis with partial pruning and/or from dilation of immature vessels due to the lack of vascular smooth muscle cells in their walls.
“This may have resulted either from angiogenesis with partial pruning and/or from dilation of immature vessels due to the lack of vascular smooth muscle cells in their walls 42.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Carmeliet P Angiogenesis in health and disease Nat Med 2003 9 653 660 12778163
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThy1-ChR2 mice express channelrhodopsin in cortical pyramidal neurons, enabling optical control of neuronal activation.
“These mice have been bred to express channelrhodopsin-, a light-gated cation channel that is non-selective towards H+, Na+, K+, and CA2+, in cortical pyramidal neurons, enabling optical control of neuronal activation 19,20.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [19] Nagel G Szellas T Huhn W Kateriya S Adeishvili N Berthold P Channelrhodopsin-2, a directly light-gated cation-selective membrane channel Proceedings of the National Academy of Sciences 2003 100 13940 13945 PMC283525 14615590
Not checked in the free run.
- cites [20] Arenkiel BR Peca J Davison IG Feliciano C Deisseroth K Augustine GJ In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2 Neuron 2007 54 205 218 17442243 PMC3634585
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe age of 9-week-old mice is considered equivalent to puberty/young adulthood in humans.
“This age is considered equivalent to puberty/young adulthood in humans 18.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Agoston DV How to translate time? The temporal aspect of human and rodent biology Front Neurol 2017 8 92 28367138 PMC5355425
Not checked in the free run.
May combine two claims.
InterpretationreasoningImpairments of cerebrovascular circulation and altered neuronal function may have produced an imbalance between the metabolic demands of the tissue and the brain's ability to deliver metabolites.
“Impairments of the cerebrovascular circulation as well as altered neuronal function may have produced an imbalance between the metabolic demands of the tissue and the brain's ability to deliver these metabolites.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRecent work from Tucker et al. suggests that behavioural outcomes between female and male C57BL/6J mice post TBI are equivalent.
“recent work from Tucker et al. suggests that behavioural outcomes between female and male C57BL/6J mice post TBI are equivalent 33.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Tucker LB Fu AH McCabe JT Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research J Neurotrauma 2016 33 880 894 25951234 PMC4860656
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe reduction in amplitude of evoked responses suggests fewer viable neurons and/or impaired functioning of the surviving neurons.
“The signals detected with these extracellular recordings are an integration of neuronal depolarizations that occur proximal to the electrodes; reduction in the amplitude of evoked responses suggests fewer viable neurons and/or impaired functioning of the surviving neurons.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationRodents may reach sexual maturity around 50 days of age but do not enter adulthood until 210 days; hence, the mice in this study are sexually mature but not yet adults.
“They suggest that rodents may reach sexual maturity around 50 days of age, but do not enter adulthood until 210 days; hence, the mice in this study are sexually mature but not yet adults.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [18] Agoston DV How to translate time? The temporal aspect of human and rodent biology Front Neurol 2017 8 92 28367138 PMC5355425
Not checked in the free run.
- cites [29] Scopaz KA Hatzenbuehler JR Risk modifiers for concussion and prolonged recovery Sports Health 2013 5 537 541 24427429 PMC3806172
Not checked in the free run.
May combine two claims.
Study design and conductown dataBoth traumatic brain injury and sham mice were maintained in a stable physiological state during imaging procedures, with no significant differences between groups for any physiological parameters.
“Both TBI and sham mice were maintained in a stable physiological state during imaging procedures, as summarized in Table 3. There were no significant differences between groups for any physiological parameters.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIron depositions result in T2 tashortening, potentially explaining the hypointensities seen on T2-weighted imaging here.
“Iron depositions result in T2 tashortening, potentially explaining the hypointensities seen on T2-weighted imaging here 38.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] Wu G Xi G Hua Y Sagher O T2* magnetic resonance imaging sequences reflect brain tissue iron deposition following intracerebral hemorrhage Transl Stroke Res 2010 1 31 34 20811505 PMC2930789
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningAs the neuronal and cerebrovascular networks are closely coupled functionally, impairments of one could affect the other, and vice versa.
“As the neuronal and cerebrovascular networks are closely coupled functionally, impairments of one could affect the other, and vice versa.”
Quote in the paperNot a substantial claim- Rests on an assumption: The neuronal and cerebrovascular networks are closely coupled functionally.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe aforementioned blood velocity decrease surrounding the site of the injury could have also contributed to the observed elongation of arterial transit time.
“The aforementioned blood velocity decrease surrounding the site of the injury could have also contributed to the observed elongation of arterial transit time.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningGlobal reduction of cerebrovascular reactivity could result from increased intracranial pressure or be secondary to global decreases in neuronal activity and thus their signaling to the vessels.
“Global reduction of cerebrovascular reactivity could result from increased intracranial pressure or be secondary to global decreases in neuronal activity and thus their signaling to the vessels.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThis is the first study to employ optogenetic photostimulation as a readout of neuronal function following TBI.
“To our knowledge, ours is the first study to employ optogenetic photostimulation as a readout of neuronal function following TBI.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationClinical repeated TBI is known to impair cerebrovascular reactivity, but this had not previously been observed in experimental repeated TBI.
“While clinical repeated TBI is known to impair cerebrovascular reactivity, this had not previously been observed in experimental repeated TBI 49,50.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [49] Mutch WAC Ellis MJ Ryner LN Ruth Graham M Dufault B Gregson B Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome J Neurosurg 2016 125 648 660 26684777
Not checked in the free run.
- cites [50] Ellis MJ Ryner LN Sobczyk O Fierstra J Mikulis DJ Fisher JA Neuroimaging assessment of cerebrovascular reactivity in concussion: Current concepts, methodological considerations, and review of the literature Front Neurol 2016 7 61 27199885 PMC4850165
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationElevated peri-contusional vascular density and altered topology of the vessel network have also been seen in animal models of moderate to severe TBI; this remodelling has been suggested to underlie changes in the neurovascular unit functioning.
“an elevated peri-contusional vascular density and altered topology of the vessel network have also been seen in animal models of moderate to severe TBI 44,46: this remodelling has been suggested to underlie changes in the neurovascular unit functioning 53.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [44] Hayward NMEA Tuunanen PI Immonen R Ndode-Ekane XE Pitkänen A Gröhn O Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats J Cereb Blood Flow Metab 2011 31 166 177 20485295 PMC3049481
Not checked in the free run.
- cites [46] Obenaus A Ng M Orantes AM Kinney-Lang E Rashid F Hamer M Traumatic brain injury results in acute rarefication of the vascular network Sci Rep 2017 7 239 28331228 PMC5427893
Not checked in the free run.
- cites [53] Jullienne A Obenaus A Ichkova A Savona-Baron C Pearce WJ Badaut J Chronic cerebrovascular dysfunction after traumatic brain injury J Neurosci Res 2016 94 609 622 27117494 PMC5415378
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOstergaard et al. proposed that moderate TBI could lead to an increase in heterogeneity of capillary transit times.
“Ostergaard et al. proposed that moderate TBI could lead to an increase in heterogeneity of capillary transit times 45.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] Østergaard L Engedal TS Aamand R Mikkelsen R Iversen NK Anzabi M Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury J Cereb Blood Flow Metab 2014 34 1585 1598 25052556 PMC4269727
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHayward et al. observed acute reduction of vessel density followed by a chronic stage increase in vessel density on rat endothelial cell antibody-1 immunohistochemistry in a lateral fluid percussive model of moderate TBI in rats.
“Hayward et al., observed acute reduction of vessel density followed by a chronic stage increase in vessel density on rat endothelial cell antibody-1 immunohistochemistry in a lateral fluid percussive model of moderate TBI in rats 44.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Hayward NMEA Tuunanen PI Immonen R Ndode-Ekane XE Pitkänen A Gröhn O Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats J Cereb Blood Flow Metab 2011 31 166 177 20485295 PMC3049481
Not checked in the free run.
May combine two claims.
InterpretationcitationCerebrovascular reactivity impairment was due to the newly sprouted vessels seen on in vivo two-photon fluorescence microscopy that were not yet functionally mature, hence having thin vessel walls and limited endothelium-associated smooth muscle cells.
“we postulate that cerebrovascular reactivity impairment was due to the newly sprouted vessels seen on in vivo two-photon fluorescence microscopy that were not yet functionally mature, hence having thin vessel walls 52 and limited endothelium-associated smooth muscle cells 42.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [52] Pries AR Reglin B Secomb TW Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli Hypertension 2005 46 725 731 16172421
Not checked in the free run.
- cites [42] Carmeliet P Angiogenesis in health and disease Nat Med 2003 9 653 660 12778163
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAn earlier study in a model of moderate TBI reported decreased electrophysiological responses to contralateral forepaw stimulation two weeks following a single controlled cortical impact.
“an earlier study in a model of moderate TBI reported decreased electrophysiological responses to contralateral forepaw stimulation two weeks following a single controlled cortical impact 58.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] Li N Yang Y Glover DP Zhang J Saraswati M Robertson C Evidence for impaired plasticity after traumatic brain injury in the developing brain J Neurotrauma 2014 31 395 403 24050267 PMC3922417
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationnone givenPhotostimulation of opsin-expressing cells affords two important advantages over peripheral stimulation: finer spatial targeting of the neuronal perturbation in relation to the site of the injury and cell-type specific activation.
“Photostimulation of opsin-expressing cells affords two important advantages over peripheral stimulation in that it enables finer spatial targeting of the neuronal perturbation in relation to the site of the injury as well as cell-type specific activation.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationMild impact may cause subtle dendritic and axonal damage, thus altering connections between cortical neurons; fewer recruited neurons following photostimulation could thus also have contributed to the observed decrease in evoked response amplitude.
“Mild impact may cause subtle dendritic and axonal damage, thus altering connections between cortical neurons: fewer recruited neurons following photostimulation could thus also have contributed to the observed decrease in evoked response amplitude 59.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] Sword J Masuda T Croom D Kirov SA Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging Brain 2013 136 1446 1461 23466395 PMC3634194
Not checked in the free run.
May combine two claims.
InterpretationreasoningGiven that there was no statistically significant effect of the serial impacts on neuronal survival, the reduction of evoked response amplitude may be a result of impaired responses on the individual unit level.
“Given that there was no statistically significant effect of the serial impacts on neuronal survival (on NeuN, MAP2, and neurofilament immunofluorescence), the reduction of evoked response amplitude may be a result of impaired responses on the individual unit level.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationA dearth of available metabolites may also lead to neuronal dysfunction and loss.
“A dearth of available metabolites may also lead to neuronal dysfunction and loss 28”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Baron J-C Yamauchi H Fujioka M Endres M Selective neuronal loss in ischemic stroke and cerebrovascular disease J Cereb Blood Flow Metab 2014 34 2 18 24192635 PMC3887360
Not checked in the free run.
May combine two claims.
PremisecitationEnhanced GFAP fluorescence is sometimes also associated with astrocytic swelling, which has been observed to reduce capillary lumen and in turn reduce cerebral blood flow and microvascular hematocrit.
“Enhanced GFAP fluorescence is sometimes also associated with astrocytic swelling, which has been observed to reduce capillary lumen and in turn reduce cerebral blood flow and microvascular hematocrit 56.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [56] Bouzat P Millet A Boue Y Pernet-Gallay K Trouve-Buisson T Gaide-Chevronnay L Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin Crit Care Med 2013 41 1316 1324 23591210
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEnhancement of GFAP has been previously reported in the acute phase of repeated TBI as part of the neuroinflammatory cascade.
“Enhancement of GFAP has been previously reported in the acute phase of repeated TBI as part of the neuroinflammatory cascade 54.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [54] Bolton AN Saatman KE Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals J Neuropathol Exp Neurol 2014 73 933 947 25232942 PMC4170569
Not checked in the free run.
The paper relies on this without support.
A mismatch between metabolic demands and the brain's ability to deliver metabolites is key in the pathological progression of moderate to severe traumatic brain injury.
“This mismatch has been identified as key in the pathological progression of moderate to severe TBI.”
The paper relies on this without support.
Impairment of cerebrovascular reactivity leads to cognitive dysfunction and can contribute to functional deficits in repeated traumatic brain injury patients.
“Impairment of CVR is known to lead to cognitive dysfunction and hence could contribute to the functional deficits seen in repeated TBI patients.”
The paper relies on this without support.
Cerebrovascular reactivity is a critical aspect of healthy brain function because the brain depends on tuning of blood flow to local tissue metabolic needs.
“Cerebrovascular reactivity is a critical aspect of healthy brain function as the brain depends on tuning of blood flow to the local tissue metabolic needs.”
The paper relies on this without support.
Transcallosal connections between homologous regions of the cortex are dense.
“Given the density of transcallosal connections between homologous regions of the cortex”
The paper relies on this without support.
The neuronal and cerebrovascular networks are closely coupled functionally.
“As the neuronal and cerebrovascular networks are closely coupled functionally”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Contrary to studies showing vascular dysfunction in mTBI, we did not see evidence of cellular senescence in endothelial cells.
“Contrary to studies showing vascular dysfunction in mTBI [2, 157], we did not see evidence of cellular senescence in endothelial cells.”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [2]
Cites
Fitting Linear Mixed-Effects Models Using lme4Preprint
Bates, D. M., Maechler, M., Bolker, B. M., & Walker, S. (2014) · arXiv (Cornell University) · doi:10.3929/ethz-b-000105397 · Cited by 9,435 · see citing works
Generalized linear mixed models: a practical guide for ecology and evolution
Bolker, B. M., Brooks, M. E., Clark, C. J., Geange, S. W., Poulsen, J. R., Stevens, M. H. H., & White, J.-S. S. (2009) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2008.10.008 · Cited by 8,910 · see citing works
Angiogenesis in health and disease
Carmeliet, P. (2003) · Nature Medicine · doi:10.1038/nm0603-653 · Cited by 4,258 · see citing works
Channelrhodopsin-2, a directly light-gated cation-selective membrane channel
Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P. R., Ollig, D., Hegemann, P., & Bamberg, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1936192100 · Cited by 2,672 · see citing works
Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury
McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., Santini, V. E., Lee, H.-S., Kubilus, C. A., & Stern, R. A. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9d503 · Cited by 2,295 · see citing works
The spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
RARE imaging: A fast imaging method for clinical MR
Hennig, J., Nauerth, A., & Friedburg, H. (1986) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910030602 · Cited by 2,088 · see citing works
Cassidy, J. D., Carroll, L., Peloso, P. M. J., Borg, J., von Holst, H., Holm, L. W., Kraus, J. F., & Coronado, V. G. (2004) · Journal of Rehabilitation Medicine · doi:10.1080/16501960410023732 · Cited by 1,612 · see citing works
The New Neurometabolic Cascade of Concussion
Giza, C. C., & Hovda, D. A. (2014) · Neurosurgery · doi:10.1227/neu.0000000000000505 · Cited by 1,353 · see citing works
Unterberg, A. W., Stover, J., Kress, B., & Kiening, K. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.06.046 · Cited by 881 · see citing works
Arenkiel, B. R., Peca, J., Davison, I. G., Feliciano, C., Deisseroth, K., Augustine, G. J., Ehlers, M. D., & Feng, G. (2007) · Neuron · doi:10.1016/j.neuron.2007.03.005 · Cited by 755 · see citing works
Mittl, R. L., Grossman, R. I., Hiehle, J. F., Hurst, R. W., Kauder, D. R., Gennarelli, T. A., & Alburger, G. W. (1994) · PubMed Central · Cited by 435 · see citing works
Meaney, D. F., & Smith, D. H. (2010) · Clinics in Sports Medicine · doi:10.1016/j.csm.2010.08.009 · Cited by 428 · see citing works
Temporal Window of Vulnerability to Repetitive Experimental Concussive Brain Injury
Longhi, L., Saatman, K., Fujimoto, S. T., Raghupathi, R., Meaney, D., Davis, J. E., McMillan, A., Conte, V., Laurer, H., Stein, S., et al. (2005) · Neurosurgery · doi:10.1227/01.neu.0000149008.73513.44 · Cited by 336 · see citing works
Mouzon, B., Bachmeier, C. J., Ferro, A., Ojo, J., Crynen, G. C., Acker, C. M., Davies, P., MULLAN, M. J., Stewart, W. B., Jr., & Crawford, F. (2013) · Annals of Neurology · doi:10.1002/ana.24064 · Cited by 331 · see citing works
Mild head injury increasing the brain's vulnerability to a second concussive impact
Laurer, H. L., Bareyre, F. M., Lee, V. M. Y. C., Trojanowski, J. Q., Longhi, L., Hoover, R., Saatman, K. E., Raghupathi, R., Hoshino, S., Grady, M. S., et al. (2001) · Journal of Neurosurgery · doi:10.3171/jns.2001.95.5.0859 · Cited by 313 · see citing works
Mouzon, B., Chaytow, H., Crynen, G. C., Bachmeier, C. J., Stewart, J., MULLAN, M. J., Stewart, W. B., Jr., & Crawford, F. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2498 · Cited by 294 · see citing works
Cerebral Vascular Injury in Traumatic Brain Injury
Kenney, K., Amyot, F., Haber, M., Pronger, A. M., Bogoslovsky, T., Moore, C. B., & Diaz-Arrastia, R. R. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.05.019 · Cited by 272 · see citing works
Post-traumatic stress disorder vs traumatic brain injury
Bryant, R. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.2/rbryant · Cited by 268 · see citing works
Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease
Baron, J., Yamauchi, H., Fujioka, M., & Endres, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.188 · Cited by 232 · see citing works
How to Translate Time? The Temporal Aspect of Human and Rodent Biology
Agoston, D. V. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00092 · Cited by 226 · see citing works
Pries, A. R., Reglin, B., & Secomb, T. W. (2005) · Hypertension · doi:10.1161/01.hyp.0000184428.16429.be · Cited by 225 · see citing works
Repeated Mild Traumatic Brain Injury
Fehily, B., & Fitzgerald, M. (2017) · Cell Transplantation · doi:10.1177/0963689717714092 · Cited by 223 · see citing works
Traumatic brain injury and Alzheimer's disease: a review
van den Heuvel, C., Thornton, E., & Vink, R. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)61021-2 · Cited by 213 · see citing works
Increased Risk of Dementia in Patients with Mild Traumatic Brain Injury: A Nationwide Cohort Study
Lee, Y., Hou, S., Lee, C., Hsu, C., Huang, Y.-S., & Su, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062422 · Cited by 204 · see citing works
Parkes, L. M., & Tofts, P. S. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10180 · Cited by 203 · see citing works
Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice
Ojo, J.-O., Mouzon, B., Greenberg, M. B., Bachmeier, C., Mullan, M., & Crawford, F. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182814cdf · Cited by 166 · see citing works
Tucker, L. B., Fu, A. H., & McCabe, J. T. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.3977 · Cited by 162 · see citing works
Capillary Transit Time Heterogeneity and Flow-Metabolism Coupling after Traumatic Brain Injury
Østergaard, L., Engedal, T. S., Aamand, R., Mikkelsen, R., Iversen, N., Anzabi, M., Næss‐Schmidt, E. T., Drasbek, K. R., Bay, V., Blicher, J. U., et al. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.131 · Cited by 147 · see citing works
Pharmacologically-Induced Neurovascular Uncoupling is Associated with Cognitive Impairment in Mice
Tarantini, S., Hertelendy, P., Tucsek, Z., Valcarcel‐Ares, M. N., Smith, N., Menyhárt, Á., Farkas, E., Hodges, E. L., Towner, R. A., Deák, F., et al. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.162 · Cited by 143 · see citing works
Chronic cerebrovascular dysfunction after traumatic brain injury
Jullienne, A., Obenaus, A., Ichkova, A., Savona‐Baron, C., Pearce, W. J., & Badaut, J. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23732 · Cited by 138 · see citing works
Bey, T. A., & Ostick, B. (2009) · PubMed Central · Cited by 128 · see citing works
Risk Modifiers for Concussion and Prolonged Recovery
Scopaz, K. A., & Hatzenbuehler, J. R. (2013) · Sports Health A Multidisciplinary Approach · doi:10.1177/1941738112473059 · Cited by 109 · see citing works
Springer Handbook of Bio-/Neuroinformatics
Liang, L., Krishnamurthi, R., Kasabov, N. K., & Feigin, V. (2013) · Springer handbooks · doi:10.1007/978-3-642-30574-0 · Cited by 98 · see citing works
Repetitive Mild Traumatic Brain Injury Causes Optic Nerve and Retinal Damage in a Mouse Model
Tzekov, R. T., Quezada, A., Gautier, M. K., Biggins, D., Frances, C., Mouzon, B., Jamison, J. A., MULLAN, M. J., & Crawford, F. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000059 · Cited by 92 · see citing works
Ellis, M. J., Ryner, L. N., Sobczyk, O., Fierstra, J., Mikulis, D. J., Fisher, J. A., Duffin, J., & Mutch, W. A. C. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00061 · Cited by 88 · see citing works
Bolton, A. N., & Saatman, K. E. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000115 · Cited by 86 · see citing works
Vazquez, A. L., Fukuda, M., Crowley, J. C., & Kim, S.-G. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht147 · Cited by 85 · see citing works
Correlation of CD34 + Cells with Tissue Angiogenesis after Traumatic Brain Injury in a Rat Model
Guo, X., Liu, L., Zhang, M., Bergeron, A. L., Cui, Z., Dong, J.-F., & Zhang, J. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2008.0733 · Cited by 83 · see citing works
Sword, J., Masuda, T., Croom, D., & Kirov, S. A. (2013) · Brain · doi:10.1093/brain/awt026 · Cited by 81 · see citing works
Morgan, R., Kreipke, C. W., Roberts, G. G., Bagchi, M., & Rafols, J. A. (2007) · Neurological Research · doi:10.1179/016164107x204693 · Cited by 80 · see citing works
Hayward, N., Tuunanen, P. I., Immonen, R. J., Ndode‐Ekane, X. E., Pitkänen, A., & Gröhn, O. H. J. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.67 · Cited by 77 · see citing works
Traumatic brain injury results in acute rarefication of the vascular network
Obenaus, A., Ng, M. T., Orantes, A. M., Kinney‐Lang, E., Rashid, F. M., Hamer, M., DeFazio, R. A., Tang, J., Zhang, J. H., & Pearce, W. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-00161-4 · Cited by 73 · see citing works
Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome
Mutch, W. A. C., Ellis, M. J., Ryner, L. N., Graham, M. R., Dufault, B., Gregson, B. P., Hall, T., Bunge, M. K., & Essig, M. (2015) · Journal of neurosurgery · doi:10.3171/2015.6.jns15972 · Cited by 71 · see citing works
Zeidan, F. Z., & Johnson, S. K. (2010) · Springer eBooks · doi:10.1007/978-0-387-79948-3_572 · Cited by 69 · see citing works
Yang, Z., Wang, P., Morgan, D., Bruijnzeel, A. W., Lin, D., Pan, J., Lin, F. Y., Strang, K. H., Selig, T. M., Pérez, P. D., et al. (2015) · Scientific Reports · doi:10.1038/srep11178 · Cited by 68 · see citing works
Hirschler, L., Debacker, C., Voiron, J., Köhler, S., Warnking, J. M., & Barbier, E. (2017) · Magnetic Resonance in Medicine · doi:10.1002/mrm.26767 · Cited by 58 · see citing works
Self-citationWu, G., Xi, G., Hua, Y., & Sagher, O. (2010) · Translational Stroke Research · doi:10.1007/s12975-009-0008-6 · Cited by 54 · see citing works
Imaging of Cerebrovascular Function in Chronic Traumatic Brain Injury
Amyot, F., Kenney, K., Moore, C. B., Haber, M., Turtzo, L. C., Shenouda, C. N., Silverman, E., Gong, Y., Qu, B., Harburg, L., et al. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2017.5114 · Cited by 53 · see citing works
Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain
Li, N., Yang, Y., Glover, D. P., Zhang, J., Saraswati, M., Robertson, C., & Pelled, G. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.3059 · Cited by 48 · see citing works
Sex Differences in Working Memory after Mild Traumatic Brain Injury: A Functional MR Imaging Study
Hsu, H.-L., Chen, D. Y.-T., Tseng, Y.-C., Kuo, Y.-S., Huang, Y.-L., Chiu, W.-T., Yan, F.-X., Wang, W.-S., & Chen, C.-J. (2015) · Radiology · doi:10.1148/radiol.2015142549 · Cited by 47 · see citing works
Role of functional imaging in neurological disorders
Weiller, C., May, A., Sach, M., Buhmann, C., & Rijntjes, M. (2006) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20591 · Cited by 45 · see citing works
Repeated Mild Closed Head Injury Impairs Short-Term Visuospatial Memory and Complex Learning
Hylin, M. J., Orsi, S. A., Rozas, N. S., Hill, J. L., Zhao, J., Redell, J. B., Moore, A. N., & Dash, P. K. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2012.2717 · Cited by 43 · see citing works
Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries
Velosky, A. G., Tucker, L. B., Fu, A. H., Liu, J., & McCabe, J. T. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.02.017 · Cited by 36 · see citing works
Donovan, V., Bianchi, A., Hartman, R. E., Bhanu, B., Carson, M. J., & Obenaus, A. (2012) · NeuroImage Clinical · doi:10.1016/j.nicl.2012.08.001 · Cited by 35 · see citing works
Bouzat, P., Millet, A., Boué, Y., Pernet‐Gallay, K., Trouvé-Buisson, T., Gaide‐Chevronnay, L., Barbier, E., & Payen, J. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31827ca64e · Cited by 29 · see citing works
Self-citationFerguson, S. A., Mouzon, B., Lynch, C., Lungmus, C., Morin, A., Crynen, G. C., Carper, B. A., Bieler, G. S., Mufson, E. J., Stewart, W. B., Jr., et al. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00416 · Cited by 28 · see citing works
Glucose Tightly Controls Morphological and Functional Properties of Astrocytes
Lee, C.-Y., Dallérac, G. M., Ezan, P., Anděrová, M., & Rouach, N. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00082 · Cited by 25 · see citing works
Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition
Lake, E. M. R., Mester, J. R., Thomason, L. A. M., Adams, C., Bazzigaluppi, P., Koletar, M. M., Janik, R., Carlen, P. L., McLaurin, J., Stanisz, G. J., et al. (2016) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25541 · Cited by 11 · see citing works
Self-citationRepeated mild traumatic brain injury: potential mechanisms of damage
(2016) · Cell Transplantation · doi:10.3727/096368916x692807 · Cited by 10 · see citing works
Sex Differences in Working Memory after Mild Traumatic Brain Injury: A Functional MR Imaging Study
Hsu, H.-L., Chen, D. Y. T., Tseng, Y.-C., Kuo, Y.-S., Huang, Y., Chiu, W.-T., Feng-xian, Y., Wang, W.-S., & Chen, C. (2016) · Radiology · doi:10.1148/radiol.2016164022 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 62 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Catalytic patch with redox Cr/CeO 2 nanozyme of noninvasive intervention for brain trauma
Zhang, S., Liu, Y., Sun, S., Wang, J., Li, Q., Yan, R., Gao, Y., Liu, H., Liu, S., Hao, W., et al. (2021) · Theranostics · doi:10.7150/thno.51912 · Cited by 114 · see citing works
Wu, Y., Wu, H., Guo, X., Pluimer, B. R., & Zhao, Z. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01030 · Cited by 82 · see citing works
DNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Schwab, N., Grenier, K., & Hazrati, L.-N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0822-3 · Cited by 47 · see citing works
Li, L., Liang, J., & Fu, H. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.020 · Cited by 41 · see citing works
Mimicking Extracellular Matrix via Engineered Nanostructured Biomaterials for Neural Repair
Raspa, A., & Gelain, F. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666201111111102 · Cited by 32 · see citing works
Czigler, A., Tóth, L., Szarka, N., Berta, G., Amrein, K., Czeiter, E., Lendvai-Emmert, D., Bodó, K., Tarantini, S., Koller, Á., et al. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2019.6439 · Cited by 32 · see citing works
Jin, X., Wang, Z., Xu, H., Liu, C., Wei, Z., Zhao, L., & Ren, L. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29515 · Cited by 23 · see citing works
Joo, I. L., Lam, W. W., Oakden, W., Hill, M. E., Koletar, M. M., Morrone, C. D., Stanisz, G. J., McLaurin, J., & Stefanovic, B. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102327 · Cited by 23 · see citing works
Self-citationSaikia, B. B., Bhowmick, S., Malat, A., Rani, M. R. P., Thaha, A., & Muneer, P. M. A. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1742-23.2024 · Cited by 24 · see citing works
Xia, X., Zhou, C., Sun, X., He, X., Liu, C., & Wang, G. (2020) · Brain and Behavior · doi:10.1002/brb3.1777 · Cited by 16 · see citing works
Mester, J. R., Bazzigaluppi, P., Dorr, A. E., Beckett, T. L., Burke, M. J., McLaurin, J., Sled, J. G., & Stefanovic, B. (2021) · Theranostics · doi:10.7150/thno.60190 · Cited by 14 · see citing works
Self-citationOptogenetics for Understanding and Treating Brain Injury: Advances in the Field and Future Prospects
Sun, Y., Li, M., Cao, S., Xu, Y., Wu, P., Xu, S., Pan, Q., Guo, Y., Ye, Y., Wang, Z., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031800 · Cited by 14 · see citing works
Advances in Optogenetics Applications for Central Nervous System Injuries
Geng, Y., Li, Z., Zhu, J., Du, C., Yuan, F., Cai, X., Ali, A., Yang, J., Tang, C., Cong, Z., et al. (2022) · Journal of Neurotrauma · doi:10.1089/neu.2022.0290 · Cited by 12 · see citing works
Repeated mild traumatic brain injuries impair visual discrimination learning in adolescent mice
Pinkowski, N. J., Guerin, J., Zhang, H., Carpentier, S. T., McCurdy, K. E., Pacheco, J. M., Mehos, C. J., Brigman, J. L., & Morton, R. A. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107315 · Cited by 11 · see citing works
Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition
Lake, E. M. R., Mester, J. R., Thomason, L. A. M., Adams, C., Bazzigaluppi, P., Koletar, M. M., Janik, R., Carlen, P. L., McLaurin, J., Stanisz, G. J., et al. (2016) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25541 · Cited by 11 · see citing works
Self-citationRosen, G. A., Kirsch, D. A., Horowitz, S., Cherry, J. D., Nicks, R., Kelley, H. J., Uretsky, M., Dell’Aquila, K., Mathias, R., Cormier, K., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01612-y · Cited by 9 · see citing works
Poster Viewing Sessions PB01-B01 to PB03-V09
Badji, A., de la Colina, A. N., Sabra, D., Karakuzu, A., Bherer, L., Lamarre-Cliche, M., Stikov, N., Gauthier, C. J., Cohen‐Adad, J., & Girouard, H. (2019) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x19851020 · Cited by 8 · see citing works
Penn, C., Katnik, C. P., Cuevas, J., Mohapatra, S. S., & Mohapatra, S. (2023) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2023.109876 · Cited by 7 · see citing works
Optogenetic Modulation for the Treatment of Traumatic Brain Injury
Delaney, S. L., Gendreau, J. L., D’Souza, M., Feng, A. Y., & Ho, A. L. (2019) · Stem Cells and Development · doi:10.1089/scd.2019.0187 · Cited by 8 · see citing works
Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury
Singh, A., Gong, S., Vu, A., Li, S., & Obenaus, A. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01840-w · Cited by 5 · see citing works
Bazzigaluppi, P., Mester, J. R., Joo, I. L., Weisspapir, I., Dorr, A. E., Koletar, M. M., Beckett, T. L., Khosravani, H., Carlen, P. L., & Stefanovic, B. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x211013656 · Cited by 5 · see citing works
Self-citationBrett, B. L., Cohen, A. D., McCrea, M., & Wang, Y. (2023) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103538 · Cited by 5 · see citing works
Steinman, J., Cahill, L. S., Stortz, G., Macgowan, C. K., Stefanovic, B., & Sled, J. G. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6872 · Cited by 5 · see citing works
Self-citationBlaschke, S. J., Rautenberg, N., Endepols, H., Jendro, A., Konrad, J., Vlachakis, S., Wiedermann, D., Schroeter, M., Hoffmann, B., Merkel, R., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094837 · Cited by 4 · see citing works
Dunn, C., Ferreira, L. A., Venier, S. M., Ali, S. F., Wolchok, J. C., & Balachandran, K. (2022) · Neurotrauma Reports · doi:10.1089/neur.2021.0059 · Cited by 6 · see citing works
Shafqat, Q., Christensen, J., Hamilton, A. M., Imhof, E., Mychasiuk, R., & Dunn, J. F. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00307 · Cited by 3 · see citing works
Longitudinal, Multiparametric MRI Assessment of repetitive mild TBI in ratsPreprint
Khan, A. R., Hansen, B., Iversen, N. K., Olesen, J. L., Angoa‐Pérez, M., Kuhn, D. M., Østergaard, L., & Jespersen, S. N. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/666024 · Cited by 3 · see citing works
Rozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Patel, S., Koletar, M. M., Hill, M. E., McLaurin, J., Goubran, M., & Stefanovic, B. (2024) · eLife · doi:10.7554/elife.95525 · Cited by 2 · see citing works
Self-citationEed, A., Hamilton, J., Xu, X., Geremia, N. M., Prado, V. F., Prado, M. A. M., Baron, C. A., Menon, R. S., & Brown, A. M. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02183-w · Cited by 2 · see citing works
Brain microvascular endothelial cells: Beyond a barrier
Ou, J. T., Hou, K., Fu, Y., Luo, Y., Yu, Q., Shen, M., Jiang, S., Zhu, J., Wang, Y., Lin, K., et al. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261454263 · Cited by 1 · see citing works
Optogenetic Interrogation of Circuits Following Neurotrauma
Ceto, S., & Courtine, G. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.803856 · Cited by 1 · see citing works
Rozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Patel, S. B., Koletar, M. M., Hill, M. E., McLaurin, J., Goubran, M., & Stefanovic, B. (2026) · eLife · doi:10.7554/elife.95525.5 · Cited by 1 · see citing works
Self-citationRozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Patel, S. B., Koletar, M. M., Hill, M. E., McLaurin, J., Goubran, M., & Stefanovic, B. (2024) · doi:10.7554/elife.95525.2 · Cited by 1 · see citing works
Self-citationDelayed cerebrovascular dysfunction and social deficits after traumatic brain injuryPreprint
Singh, A., Gong, S., Vu, A., Li, S., & Obenaus, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.15.580515
Rozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Goubran, M., & Stefanovic, B. (2024) · doi:10.7554/elife.95525.1
Self-citationBaskaran, A., Hoehn, R. D., & Rose, C. G. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13247648
Rozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Patel, S. B., Koletar, M. M., Hill, M. E., McLaurin, J., Goubran, M., & Stefanovic, B. (2025) · doi:10.7554/elife.95525.3
Self-citationRozak, M. W., Mester, J. R., Attarpour, A., Dorr, A. E., Patel, S. B., Koletar, M. M., Hill, M. E., McLaurin, J., Goubran, M., & Stefanovic, B. (2025) · eLife · doi:10.7554/elife.95525.4
Self-citationPersistent dysmorphology and dysfunction of the brain microvasculature following repeated trauma
Dorr, A. E., Rozak, M. W., Stanisz, A. M., Joo, I. L., Ntiri, E. E., Xu, T., Bazzigaluppi, P., Mester, J. R., Sled, J. G., Goubran, M., et al. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251400242
Self-citationRosen, G. A., Kirsch, D. A., Horowitz, S., Cherry, J. D., Nicks, R., Kelley, H. J., Uretsky, M., Dell’Aquila, K., Mathias, R., Cormier, K. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26606581
Rosen, G. A., Kirsch, D. A., Horowitz, S., Cherry, J. D., Nicks, R., Kelley, H. J., Uretsky, M., Dell’Aquila, K., Mathias, R., Cormier, K. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26606587
Rosen, G. A., Kirsch, D. A., Horowitz, S., Cherry, J. D., Nicks, R., Kelley, H. J., Uretsky, M., Dell’Aquila, K., Mathias, R., Cormier, K. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26606584
Li, C.-X., Triplett, S. E., Griffin, M. N., Holberton, A. L., Kadragic, A., Moctezuma, F. G. R., Saheba, S. J., Saah, P. F., Sanz, P. I., Lee, J. C., et al. (2026) · bioRxiv · doi:10.64898/2026.02.26.708089
- Authors
- Adams, C., Bazzigaluppi, P., Beckett, T. L., Bishay, J., Weisspapir, I., Dorr, A., Mester, J. R., Steinman, J., Hirschler, L., Warnking, J. M., Barbier, E. L., McLaurin, J., Sled, J. G., & Stefanovic, B.
- Affiliations
- University of Toronto (CA)
- University Health Network (CA)
- Sunnybrook Hospital (CA)
- Inserm (FR)
- Corresponding author
- Adams, Conner
- ORCID
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2018
- Volume
- 8
- Issue
- 17
- Pages
- 4824-4836
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC6160760
- OpenAlex
- W2889661896
- Semantic Scholar
- 9af9d5874f81797cb3ca272c83c4edd9d1de1036
- Cited by
- 42
- References
- 62
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 5 · 2016: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Theranostics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc)
- Funders
- Canadian Institutes of Health Research (148521_1)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, cerebral blood flow, cerebrovascular reactivity, neuronal excitability, optogenetic stimulation, vessel density, astrocyte activation, neuronal survival
- MeSH terms
- Brain Injuries, Traumatic, Animals, Cerebrovascular Disorders, Disease Models, Animal, Magnetic Resonance Imaging, Microscopy, Fluorescence, Neuroglia, Neurons, Recurrence, Mice, Optogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
