The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index; 4 of the 15 sources its claims cite were checked for support.
Restoration of brain circulation and cellular functions hours post-mortem
Open accessAbstract
The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.
Overview
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Written from the paper’s full text.
TL;DR
The paper reports that an extracorporeal pulsatile-perfusion system (BrainEx) with a hemoglobin-based, acellular, cytoprotective perfusate restored microcirculation and selected molecular and cellular functions in intact porcine brains after 4 hours postmortem, maintained for 6 hours of ex vivo normothermic perfusion. It found preserved cytoarchitecture, reduced cell death, restored vascular/glial/synaptic and metabolic activity, but no global electrocorticographic activity.
Key findings
- After 4 h postmortem and 6 h perfusion (10 h total), BEx-perfused brains showed patent microvasculature, preserved hippocampal/neocortical/cerebellar cytoarchitecture, reduced activated caspase 3, and maintained neuronal, glial, and myelin architecture compared with 10 h PMI and control-perfusate brains.
- BEx restored vascular dilatory response to nimodipine, glial inflammatory response to LPS (increased IL-1α, IL-1β, IL-6, and IL-8 relative to other conditions), spontaneous excitatory postsynaptic currents, and active cerebral metabolism.
- At normothermia, average oxygen and glucose expenditure was approximately 2 mL/min/100 g and 6.5 mg/min/100 g tissue, respectively, with an arteriovenous lactate gradient of approximately −1 mmol/L.
- Hippocampal CA3 pyramidal neurons after BEx perfusion had membrane capacitance 125±43 pF, input resistance 195±63 MΩ, membrane time constant 32.3±8.4 ms, resting potential −71.2±7.0 mV, spike threshold −48±0.6 mV, spike amplitude 80.3±6.1 mV, and spike duration 1.58±0.24 ms; global ECoG remained isoelectric.
Methods
- Isolated, largely ex cranio porcine brains from 6–8 month old domestic pigs were perfused 4 h postmortem for 6 h under normothermic ex vivo conditions using a custom pulsatile-perfusion system and either control perfusate or BEx perfusate; comparison groups were unperfused 10 h PMI and flushed 1 h PMI.
- The study used approximately 300 post-mortem pig brains during technology development, with 32 independent brains undergoing BEx perfusion for the reported data; analyses included ultrasonography, micro-CT angiography, MRI, histology/immunohistochemistry, electron microscopy, patch-clamp electrophysiology, ECoG, LPS-induced cytokine/chemokine multiplex assays, and arteriovenous metabolic measurements.
- Data are reported as means ± SEM and analyzed with two-tailed paired/unpaired t-tests, one-way ANOVA with Dunnett’s post hoc, Kruskal-Wallis with Benjamini-Krieger-Yekutieli post hoc, or Chi-square tests, with significance set at P ≤ 0.05.
Limitations
- The paper states that no global ECoG/EEG activity reemerged, that it is uncertain whether longer perfusion could restore global activity, and that inhibitory agents in the BEx perfusate may dampen network activity; it also states that restoration of molecular/cellular processes should not be extrapolated to normal brain function or awareness.
- The paper states that delayed cellular death starting 72 h to weeks after ischemia cannot be excluded, that younger animals may have greater resilience to anoxic injury, and that further development, optimization, longer perfusion studies, and ethical standard operating procedures are needed.
- Evident from the text: this is an isolated ex vivo porcine brain model without integrated brain function, and several analyses rely on representative images or small independent-brain sample sizes (e.g., n=3 for some imaging/EM/electrophysiology experiments), which limits generalization.
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Verification
Claims the paper makes
91 Own result · 39 Own method · 17 Own interpretation · 4 Sources not found · 4 No basis given · 1 Supported so far · 1 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Under BEx-perfused conditions, the neuroanatomical structure remained intact as demonstrated by normal ventricular size, preserved gray-white matter contrast, and delineation among anatomical landmarks (Fig. 3), which were comparable to in vivo brains23–25.”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Preservation of tissue integrity
What the sources say
- Not matchedcites [23] Schmidt, V. Comparative Anatomy of the Pig Brain: an Integrative Magnetic Resonance Imaging (MRI) Study of the Porcine Brain with Special Emphasis on the External Morphology of the Cerebral Cortex. Thesis, Justus-Liebig-Universität Gießen (2015).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites [24] Conrad, M. S., Dilger, R. N. & Johnson, R. W. Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study. Dev. Neurosci. 34, 291–298 (2012). source
The citation is attached to the comparison with in vivo brains. In Material and Methods, under Image Acquisition (page not provided), the source describes obtaining brain images from living pigs by MRI; the BEx-perfusion observations are the citing authors’ own, not findings attributed to this source. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [25] Watanabe, H. et al. MR-based statistical atlas of the Göttingen minipig brain. Neuroimage 14, 1089–1096 (2001). source
boosted- Asserted: passes — The authors put it forward as true.
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- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed the presence of spontaneous excitatory postsynaptic currents (sEPSCs) at a holding potential of −70 mV”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Synaptic organization and neuronal activity
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found an increase in the percentage of nuclei positive for actCASP3 in CA1 and dentate gyrus across all control groups, indicating that the BEx formulation diminished caspase 3 activation”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Color Doppler analysis of BEx-perfused brains revealed robust flow through the major arteries of the brain”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“spontaneous global activity did not reemerge as evidence by isoelectric ECoG activity during the course of BEx perfusion”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Synaptic organization and neuronal activity
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating successful reperfusion throughout the brain via cannulation of the bilateral carotid arteries”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immunostaining for the pan-neuronal marker NeuN/RBFOX3 independently confirmed the same pattern of neuronal integrity in both hippocampal regions”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found that nearly all vessel lumens identified were filled with BEx perfusate in both the hippocampus and prefrontal neocortex”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact porcine brain under ex vivo normothermic conditions up to 4-hours postmortem.”
- Also stated in: § Microcirculation and vascular dilatory functionality · boosted
“Overall, these data demonstrate restoration and maintenance of microvascular patency and dilatory functionality for 6h following a 4h LPP.”
§ Restoration of brain circulation and cellular functions hours postmortem > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Microcirculation and vascular dilatory functionality · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantification of the proportion of cells in the CA1 field exhibiting a swollen morphology revealed a decrease under BEx perfusion, as compared to other groups”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 62
- The quote only partly states this claim. 8
- Probably not a substantial claim. 48
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Neuronal membrane capacitance (Cm=125±43 pF), input resistance (Rin=195±63 MΩ), membrane time constant (τm=32.3±8.4 ms), and membrane resting potential (Vm=−71.2±7.0 mV) were in accordance with previous values37.”
- Also stated in: § Synaptic organization and neuronal activity · plain
“the action potential parameters (spike threshold=−48±0.6 mV, spike amplitude=80.3±6.1 mV, spike duration=1.58±0.24 ms) were similar to previous literature38”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Synaptic organization and neuronal activity
What the sources say
- Partly supportedcites [37] Kowalski, J., Gan, J., Jonas, P. & Pernía-Andrade, A. J. Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats. Hippocampus 26, 668–682 (2016). https://doi.org/10.1002/hipo.22550. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says that input resistance and membrane time constant are preserved between hippocampal slices and in vivo recordings, supporting a comparison for those two properties. Table 1 (Results; page unavailable) reports cell-type-specific in vivo values for input resistance, time constant, and resting potential, but the paper does not establish that all four cited measurements—including capacitance—accord with the quoted slice values. (LLM, conf=0.84)
- Partly supportedcites [38] Simkin, D. et al. Aging-related hyperexcitability in CA3 pyramidal neurons is mediated by enhanced A-type K+ channel function and expression. J. Neurosci. 35, 13206–13218 (2015). sourceExperimental — accuracy not yet measured
Table 1 (p. 13211) reports resting potentials near the cited −71.2 mV, but input resistance is about 80–85 MΩ, not 195 MΩ. The paper does not report the cited capacitance or membrane time constant, and its brain-slice methods describe aCSF perfusion rather than BEx perfusion. Thus it supports only part of the comparison with previous values. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Also stated in: § Synaptic organization and neuronal activity · plain
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Arteriovenous gradients demonstrated consistent consumption of glucose and oxygen as the brains reached normothermia, with a concurrent production in CO2 and a physiological drop in pH39.”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Global cerebral metabolism
What the sources say
- Could not verifycites [39] Lam, T. I. et al. Intracellular pH reduction prevents excitotoxic and ischemic neuronal death by inhibiting NADPH oxidase. Proc. Natl Acad. Sci. USA 110, E4362–E4368 (2013). sourceExperimental — accuracy not yet measured
The Discussion describes neuronal acidification during ischemia and pH changes associated with physiological brain activity, but it does not report arteriovenous measurements as brains reached normothermia. Searches for arteriovenous gradients, glucose and oxygen consumption, and CO2 production found no passage addressing those observations. (LLM, conf=0.76)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“10h PMI brains exhibited a deterioration of gray-white matter contrast, reduction in LCC and APD, as well as collapse of the lateral ventricles”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Preservation of tissue integrity
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CP brains demonstrated pervasive tissue damage, decreased global signal intensity, ventricular expansion, along with increased LCC, APD, and gray-white matter contrast, indicating the presence of edema”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Preservation of tissue integrity
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis of the prefrontal neocortex also provided evidence for preservation of both neuronal cell morphology and density under BEx conditions”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under BEx conditions, we observed an increase in interleukin (IL)-1α, IL-1β, IL-6, and IL-8 relative to other conditions”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Glial structure and inflammatory functionality
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a significant and sustained increase in flow velocity post-intervention, indicating that the vasculature retained dilatory functionality in response to pharmacological stimulation”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EM analyses indicated preservation of pre-synaptic vesicular structure in BEx conditions as compared to 1h PMI, with substantial degradation in 10h PMI and CP brains”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Synaptic organization and neuronal activity
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All recorded neurons responded to supra-threshold depolarizing current stimuli with repetitive action potential firing (Fig. 6c) and expressed both voltage-gated fast Na+ currents and delayed-rectifier K+ currents (Fig. 6d).”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Synaptic organization and neuronal activity
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The epidural temperature following the craniectomy ranged from 12–15°C.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these cells displayed contracted cytoplasmic morphology and a loss of somal GAD1-positive axonal contacts”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we measured the wet-to-dry weight of cerebral samples (Fig. 3b), and observed a decrease in water content in 10h PMI controls and an increase in CP conditions, with no significant difference between 1h PMI and BEx perfusate brains”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Preservation of tissue integrity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“found a decrease in the bundle density under 10h PMI and CP conditions, demonstrating an overall deterioration of axonal architecture; in contrast, there was no difference in bundle density between 1h PMI and BEx perfusion”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these data demonstrate restoration and maintenance of microvascular patency and dilatory functionality for 6h following a 4h LPP.”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At normothermia, the average oxygen and glucose expenditure was approximately 2 mL/min/100 g and 6.5 mg/min/100 g tissue, respectively”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Global cerebral metabolism
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mitochondria in BEx perfusion conditions demonstrated normal ultrastructure”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Preservation of tissue integrity
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Assessment of neuronal density also revealed comparable values between BEx and 1h PMI controls in both CA1 and dentate gyrus, with a reduction in 10h PMI and CP conditions”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Neuronal viability and myelinated axons
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“prevents edema”
- Also stated in: § Preservation of tissue integrity · plain
“with no significant difference between 1h PMI and BEx perfusate brains”
§ Restoration of brain circulation and cellular functions hours postmortem > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Also stated in: § Preservation of tissue integrity · plain
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“our findings indicate that oxygen consumption rates were comparable with previously reported in vivo values55, but glucose consumption was higher than normal56 yet in line with rates reported for brains recovering from prolonged global ischemia57.”
§ Restoration of brain circulation and cellular functions hours postmortem > Discussion > Supplementary Discussion
What the sources say
- Not matchedcites [55]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [56]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [57]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“venous concentrations of both sodium and potassium normalized into physiological range after one hour of perfusion, potentially signaling the restoration of active Na+/K+ homeostasis”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Global cerebral metabolism
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In BEx perfusate conditions, oligodendrocytes demonstrate normal ultrastructure with numerous cisterns of rough endoplasmic reticulum (rer), and mitochondria have electron-dense matrix and many cristae.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedn = 3- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BEx and 10h PMI conditions demonstrate an increase in number of axons orthogonally oriented to the pial surface, while 1h PMI and control perfusate specimens exhibit an increase in axons oriented in more acute angles.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedcorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the hippocampal white matter of 1h PMI, 10h PMI, and control perfusate conditions, numerous cells contain segments of destroyed cytoplasm (pink), while oligodendrocytes have light cytoplasm with numerous vacuoles and swollen mitochondria (yellow); in 10h PMI samples, mitochondria may not be visible due to extensive destruction.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Micro-computed tomography angiogram (CTA) demonstrates patency of major arterial vessels as well as arterioles (left).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that neurons exhibit a swollen morphology in 1h PMI, and significant cellular destruction in 10h PMI and control perfusate conditions (arrowheads), while neurons in the BEx perfusion condition display typical elongated morphology (arrows).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Phase 1 is defined by a normal, low-resistance waveform; phase 2 displayed an increase in PSV, narrowed systole, and decreased EDV; phase 3 demonstrates decreased PSV and loss of EDV; phase 4 exhibits a reverberated “no-flow” phenomenon.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 1h PMI controls, certain mitochondria display normal ultrastructure and electron-dense matrix (m), while others exhibit a more swollen morphology (yellow).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Contrastingly, in 10h PMI conditions ependymal cells demonstrate lightened cytoplasm with numerous vacuoles (v) and swollen mitochondria (yellow). Although adherence junctions (aj) are preserved, the cell membrane is destroyed in several positions.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Power waveform analysis from a representative control perfusate brain during Phase 3 with corresponding trace (right) evidencing a MFV of 3 cm/s.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is evidence of clear cell destruction and the presence of enlarged vacuoles under 10h PMI and control perfusate conditions (arrowheads).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedcorrelationaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 is defined by a normal, low-resistance waveform; phase 2 displayed an increase in PSV, narrowed systole, and decreased EDV; phase 3 demonstrates decreased PSV and loss of EDV; phase 4 exhibits a reverberated “no-flow” phenomenon.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nissl stains (top) with higher magnification of boxed area (below) of the occipital neocortex demonstrating preserved regional cytoarchitectonics as well as neuronal structure in BEx perfused brains.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 1h PMI there is robust nuclear localization of cleaved caspase-3 across all brain regions; however, this signal decreases with increased post-mortem intervals.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pericytes and endothelial cells (highlighted semitransparent green and blue, respectively) demonstrate normal ultrastructure and contain cell nuclei (N), mitochondria (m), and cisterns of rough endoplasmic reticulum (rer). Adherence junctions between endothelial cells (aj) are visible.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
boostedn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phase 1 is defined by a normal, low-resistance waveform; phase 2 displayed an increase in PSV, narrowed systole, and decreased EDV; phase 3 demonstrates decreased PSV and loss of EDV; phase 4 exhibits a reverberated “no-flow” phenomenon.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Maximum intensity projections of the excitatory neuron marker, Neurogranin (NRGN; green), show a preservation of typical morphology of cortical pyramidal neurons under BEx perfusion (arrows), with swollen morphology under 1h PMI conditions (arrow).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An inverted pyramidal neuron structure is also appreciable under BEx perfusion (arrow).”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These compounds, as well as neuronal activity blockers, are washed out during the preparation of acute hippocampal slices for electrophysiological recordings, possibly explaining the observed discrepancy between whole cell patch-clamp recordings and global cortical activity.”
§ Restoration of brain circulation and cellular functions hours postmortem > Discussion > Supplementary Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the chamber is temperature-controlled and maintains a relative humidity level ~95% to prevent the surface of the brain from drying, since the brain is not bathed in fluid.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > BEx technology.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Global electrophysiological monitoring was performed throughout the experimental timeline.”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Overview of BEx technology
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In total, these procedures required approximately 10 mins to complete, thereby subjecting brains to this length of warm anoxia.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In all experiments, the cerebral perfusate flow was monitored and arterial pressure adjusted appropriately to maintain relatively constant cerebral flow.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For reproducibility and comparisons all measurements were conducted on pericallosal artery anterior to the genu of corpus callosum.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Ultrasonography.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“the rodent brain comprising only 14% white matter, while pig and human approximate 30 and 50%, respectively61,62.”
§ Restoration of brain circulation and cellular functions hours postmortem > Discussion > Supplementary Discussion
What the sources say
- Not matchedcites [61]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [62]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the increased plasticity in younger-aged brains may have contributed to the overall cellular recovery.”
§ Restoration of brain circulation and cellular functions hours postmortem > Discussion > Supplementary Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Due to the surgical preparation, the cranial nerves were transected and the spinal nerve roots and dorsal root ganglia were removed, which precludes potential transmission of noxious stimuli to the brain.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Global electrical activity was measured during the experimental timeline via two independent methods: commercially-available, clinical-grade BIS™ brain monitoring system (Medtronic) and 5×4 platinum-iridium electrode grid (AD-Tech; Racine, Wisconsin; Cat #: FG20C-SP10X-000) with an exposed surface of 2.8 mm and a 10 mm contact spacing covering the frontal-parieto-occipital convexity.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Global electrophysiological monitoring of the brain.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“previous work has shown that younger animals demonstrate a greater resilience to anoxic injury than adults58”
§ Restoration of brain circulation and cellular functions hours postmortem > Discussion > Supplementary Discussion
What the sources say
- Not matchedcites [58]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For all staining procedures except for intravascular hemoglobin fluorescence detection, tissue sections from each experimental group were co-stained on the same slide.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Tissue processing and histology.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that the microvasculature under BEx perfusion is patent and maintaining flow”
§ Restoration of brain circulation and cellular functions hours postmortem > Results > Microcirculation and vascular dilatory functionality
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“32 independent brains underwent BEx perfusion, data from which are presented herein.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plainn = 32- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“approximately 300 post-mortem pig brains were utilized from USDA-approved food production facilities during the process of technology development (surgical approach, vascular isolation, device configuration, perfusate formulation and so on) and the final study described herein.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Preparation and perfusion of the post-mortem porcine brain.
plainn = 300- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Figure 2 (a-c) Ultrasonography data are from a representative brain; the experiment was repeated in n = 15 independent brains with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Statistics and Reproducibility.
plainn = 15- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For quantifying fiber bundle density, three representative (8x) brightfield images were taken from each biological replicate and randomized.”
- Also stated in: § Histological data analysis and quantification. · plain
“A blinded observer counted the number of fiber bundles present per image.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Histological data analysis and quantification. · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Series resistance was always compensated by 70–80% and monitored throughout the experiment.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Brain slice electrophysiology.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Tissue sections were imaged utilizing an LSM880 confocal microscope (Zeiss; Jena, Germany) equipped with a motorized stage using 10x (0.3 NA) or 20x (0.8 NA) objective lenses with identical settings across all experimental conditions.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Microscopy and image processing.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Figure 4 (a) Images are from a representative brain per condition; the experiment was repeated in n=6 independent brains per condition with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Statistics and Reproducibility.
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Membrane voltage was corrected off-line for a calculated liquid junction potential of −10 mV.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Brain slice electrophysiology.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 41 capillaries across n=3 independent brains were analyzed.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative images were accumulated from each biological replicate from all experimental groups and randomized.”
- Also stated in: § Histological data analysis and quantification. · boosted
“Measurements were made by a blinded observer from the white matter boundary to layer 1, which could be clearly delineated by the presence of dense horizontal fibers.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
- Also stated in: § Histological data analysis and quantification. · boosted
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Image is from a representative brain; the experiment was repeated in n=3 independent brains with similar results”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A blinded observer manually counted DAPI+ objects and actCASP3+ objects utilizing the cell counter function in ImageJ software (NIH).”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from a representative brain per condition; the experiment was repeated in n=3 independent brains per condition with similar results”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from a representative brain from each condition; experiments were repeated in n=3 independent brains per group.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data are from a representative rendering; the experiment was repeated in n=3 independent brains with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For all cell marker stains, cells were excluded if below a minimum intensity level, exhibiting cellular vacuoles greater than the size of the nucleus, or demonstrating clear cellular destruction.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 54 capillaries were examined across n=3 independent brains.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Image is from a representative capillary; a total of 54 capillaries were identified across n=3 independent brains.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from a representative brain from each condition; experiments were repeated in n=3 independent brains per group with similar results.”
- Also stated in: § Extended Data · plain
“Images are from a representative brain from each condition; experiments were repeated in n=3 independent brains per group with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Also stated in: § Extended Data · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For both (a & b), images are from a representative brain from each condition; experiments were repeated in n=3 independent brains per group with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Traces are from representative brains; the experiment was repeated in n=3 independent brains for each condition with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Confocal tile scans (using the 10x or 20x objectives described above) of tissue sections stained for GFAP, IBA1, NRGN, and GAD1 were normalized to identical image surface area, randomized, and subsequently analyzed by a blinded observer for the objects of interest.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A blinded observer processed the images as described above and manually counted objects of interest and morphology utilizing the cell counter function in ImageJ software (NIH).”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Histological data analysis and quantification.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from a representative brain per condition; the experiment was repeated in n=3 independent brains with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Image is from a representative capillary; a total of 41 capillaries were identified across n=3 independent brains.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from a representative brain from each condition; experiments were repeated in n=6 independent brains per group with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Traces are from a representative brain; the experiment was repeated in n=3 independent brains with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Images are from representative brains for each brain region; experiments were repeated in n=3 independent brains per group with similar results.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Image adjustments were uniformly applied to all experimental conditions in Zeiss Zen.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Microscopy and image processing.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Pairwise comparisons by two-tailed Chi-square analysis with Yates correction with df=1 and n=786 axons were analyzed per pairwise comparison; P-values specified within; n=3 brains per condition.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Synapses in the hippocampal CA1 stratum oriens were imaged by a blind operator and 8 randomly chosen synapses per animal per condition (approximately 24 synapses/condition) were subjected to analysis by another blind observer.”
§ Restoration of brain circulation and cellular functions hours postmortem > Methods > Electron microscopy (EM).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In comparison to 1h PMI and control perfusate conditions, fluorescent signal is found in precapillary arterioles (arrowhead) and capillaries (arrow) of both 10h PMI controls and BEx perfusate, indicating that the BEx perfusate reperfuses cerebral microcirculation.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
hedgeddirectn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“n=3 measurements taken from 3 independent brains per condition.”
§ Restoration of brain circulation and cellular functions hours postmortem > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
Absence of global electrical activity detectable by BIS and ECoG indicates absence of remnant awareness.
“electrical activity was also examined to confirm that the brain did not display activity consistent with remnant awareness.”
“No such electrical activity was ever observed.”
Citations
Cites
Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging
Albers, G. W., Marks, M. P., Kemp, S. M., Christensen, S., Tsai, J. P.-C., Ortega‐Gutiérrez, S., McTaggart, R., Torbey, M., Kim‐Tenser, M. A., Leslie‐Mazwi, T. M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1713973 · Cited by 5,105
Pathobiology of ischaemic stroke: an integrated view
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01401-0 · Cited by 3,943
Cell Damage in the Brain: A Speculative Synthesis
Siesjö, B. K. (1981) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1981.18 · Cited by 1,813
Cerebral ischemia. II. The no-reflow phenomenon.
Ames, A., Rl, W., Kowada, M., Thurston, J. M., & Majno, G. (1968) · PubMed · Cited by 1,371
Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease
Kisler, K., Nelson, A. R., Montagne, A., & Zlokovic, B. V. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.48 · Cited by 1,243
The changing landscape of ischaemic brain injury mechanisms
Lee, J.-M., Zipfel, G. J., & Choi, D. W. (1999) · Nature · doi:10.1038/399a007 · Cited by 1,102
Selective vulnerability of the hippocampus in brain ischemia
Schmidt‐Kastner, R., & Freund, T. F. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90001-5 · Cited by 896
KIDNEY PRESERVATION FOR TRANSPORTATION
Collins, G. M., Bravo‐Shugarman, M., & Terasaki, P. I. (1969) · The Lancet · doi:10.1016/s0140-6736(69)90753-3 · Cited by 741
A universal scaling law between gray matter and white matter of cerebral cortex
Zhang, K., & Sejnowski, T. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090504197 · Cited by 723
A new penumbra: transitioning from injury into repair after stroke
Lo, E. H. (2008) · Nature Medicine · doi:10.1038/nm1735 · Cited by 611
Research works printed but not linked: 1
- Schmidt, V. Comparative Anatomy of the Pig Brain: an Integrative Magnetic Resonance Imaging (MRI) Study of the Porcine Brain with Special Emphasis on the External Morphology of the Cerebral Cortex. Thesis, Justus-Liebig-Universität Gießen (2015).
Cited by
Sorted by citations
Items 301–312 of 312
Directed evolution of adeno associated virus (AAV) for retinal gene therapy
Tekinsoy, M. (2022) · theses.fr (ABES) · doi:10.70675/80e7fd11z0ae7z46ffz8f69zb50f7a34df5a
Beyersdorf, F. (2026) · Asian Cardiovascular and Thoracic Annals · doi:10.1177/02184923261436888
DCD Liver Transplantation from Uncontrolled Donors
Hessheimer, A. J., Vengohechea, J., Estebánez, B., & Fondevila, C. (2026) · Springer eBooks · doi:10.1007/978-3-032-20778-4_24
Tang, B. L. (2026) · Neurological Sciences · doi:10.1007/s10072-026-09247-2
Szekeres‐Paraczky, C., Szocsics, P., Erőss, L., Mihály, O. S., & Maglóczky, Z. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146326
The Applications and Future Prospects of Organ Medicine
Zhang, J., Liu, Y., Li, Y., Hu, R., Mo, R., Zhang, Y., Huang, G., & He, X. (2026) · Health care science · doi:10.1002/hcs2.70090
Physiological Relevance of Engineered Brain Models
Servais, B., Collins, D. J., & Nisbet, D. R. (2026) · Organoids · doi:10.3390/organoids5030025
Organspende nach kontrolliertem Herzkreislaufstillstand (cDCD)
Lücking, K. M., Söffker, G., Erbguth, F., Meier, S., Neitzke, G., Westermann, S., Hahnenkamp, K., Hierundar, A., Jahnke, J., Janssens, U., et al. (2026) · Medizinische Klinik - Intensivmedizin und Notfallmedizin · doi:10.1007/s00063-026-01476-9
Serruya, M. D. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1893045
Defeating Death: The Science of Resurrection, Human Continuity, and the Future of Existence
Moussa, R. (n.d.) · PhilPapers (PhilPapers Foundation)
The role of excitotoxicity in post-cardiac arrest brain injury
Steele, A. R., Dhingra, S. J., & Sekhon, M. S. (2026) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001436
Metadata
- Authors
- Vrselja, Z., Daniele, S. G., Silbereis, J., Talpo, F., Morozov, Y. M., Sousa, A. M. M., Tanaka, B. S., Skarica, M., Pletikos, M., Kaur, N., Zhuang, Z. W., Liu, Z., Alkawadri, R., Sinusas, A. J., Latham, S. R., Waxman, S. G., & Sestan, N.
- Affiliations
- Yale University (US)
- University of Pavia (IT)
- Boston University (US)
- University of Pittsburgh (US)
- ORCID
- Venue
- Nature
- Published
- 2019-04-17
- Volume
- 568
- Issue
- 7752
- Pages
- 336-343
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6844189
- OpenAlex
- W2939414360
- Cited by
- 311
- References
- 51
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 39 · 2023: 44 · 2022: 37 · 2021: 55 · 2020: 36 · 2019: 49
- FWCI
- 41.73
- Type
- journal article
- Language
- en
- Open access
- diamond
- erevistas.uca.edu.ar
- Licence
- Locations
- Nature (publishedVersion)
- Revista de Psicología (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Repositorio Institucional UCA (Pontificia Universidad Católica Argentina) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (1s10od021845-01, 2r01mh113257-06, UL1TR001863)
- National Institute of Mental Health (#R01-MH113257, RF1MH117064)
- National Institute of General Medical Sciences (T32GM007205)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Organ Donation and Transplantation
- Keywords
- cerebral microcirculation, pulsatile perfusion, ischemia-reperfusion injury, cerebral edema, brain energy metabolism, synaptic activity, glial inflammation, cell death, pig brain, normothermic perfusion
- MeSH terms
- Animals, Autopsy, Brain, Cell Survival, Hypoxia, Brain, Cerebral Arteries, Brain Ischemia, Cerebrovascular Circulation, Disease Models, Animal, Inflammation, Microcirculation, Neuroglia, Neurons, Perfusion, Swine, Synapses, Time Factors, Vasodilation, Reperfusion Injury, Caspase 3
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.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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