The pathophysiology of traumatic brain injury at a glance

Prins, Mayumi; Greco, Tiffany; Alexander, Daya; Giza, Christopher C.

doi:10.1242/dmm.011585

Cited by 426Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

The pathophysiology of traumatic brain injury at a glance

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Prins, Mayumi, Greco, Tiffany, Alexander, Daya, Giza, Christopher C.·2013·Disease Models & Mechanisms

DOI 10.1242/dmm.011585PMC PMC3820255

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Abstract

Summary: Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson’s disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel. This increased public awareness has uncovered a number of unanswered questions concerning TBI, and we are increasingly aware of the lack of treatment options for a crisis that affects millions. Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI. Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention.

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Brainstem neurons were counted in a blinded manner using stereological procedures.
“We counted brainstem neurons in a blinded manner using the same stereological procedures as previously described.9”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [9]
The cited paper’s section on cerebral glucose metabolism discusses measurements in the brain stem, but not counts of brainstem neurons. Searches for blinded stereological procedures and neuronal counts found no passage describing the method attributed to this source. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Additional factors that may protect the brainstem include lower metabolic requirements and a blood supply less likely to be damaged by direct traumatic forces.
“Additional factors that may protect the brainstem include lower metabolic requirements and a blood supply less likely to be damaged by direct traumatic forces.9”
From Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury (2016) · cites this paper as [9]
The ‘Changes in cerebral glucose metabolism in TBI’ section mentions brain-stem glucose metabolism only in relation to levels of consciousness. The ‘Post-TBI energy crisis’ section discusses cerebral blood flow and metabolic demand generally, but does not say the brainstem has lower metabolic requirements or a blood supply less vulnerable to direct traumatic forces. Searched for brainstem, brain stem, and vascular protection from traumatic forces; our copy does not address the proposed protective factors. (LLM, conf=0.74)
Experimental — accuracy not yet measured

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Exogenous Ethyl Pyruvate versus Pyruvate during Metabolic Recovery after Oxidative Stress in Neonatal Rat Cerebrocortical Slices
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Age-dependent effects of Aroclor 1254R on calcium uptake by subcellular organelles in selected brain regions of rats
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Recent Advances in Pathophysiology of Traumatic Brain Injury
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Bidirectional Microglia–Neuron Communication in Health and Disease
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The synapse in traumatic brain injury
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The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target
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Repeated Mild Traumatic Brain Injury
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In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging
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A Systematic Review of Psychiatric, Psychological, and Behavioural Outcomes following Mild Traumatic Brain Injury in Children and Adolescents
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Alpha‐Synuclein as a Pathological Link Between Chronic Traumatic Brain Injury and Parkinson's Disease
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Altered Mitochondrial Dynamics and TBI Pathophysiology
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Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury
Hasan, A., Deeb, G., Rahal, R., Atwi, K. M., Mondello, S., Marei, H. E. S., Gali, A., & Sleiman, E. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00028 · Cited by 141 · see citing works
Traumatic brain injury: a risk factor for neurodegenerative diseases
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In Situ implantable, post-trauma microenvironment-responsive, ROS Depletion Hydrogels for the treatment of Traumatic brain injury
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Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury
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Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship
Angeloni, C., Prata, C., Sega, F. V. D., Piperno, R., & Hrelia, S. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/370312 · Cited by 133 · see citing works
Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction
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Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models
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Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments
Siedler, D. G., Chuah, M. I., Kirkcaldie, M., Vickers, J. C., & King, A. E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00429 · Cited by 113 · see citing works
Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective
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NADPH oxidases in traumatic brain injury – Promising therapeutic targets?
Ma, M. W., Wang, J., Dhandapani, K. M., Wang, R., & Brann, D. W. (2018) · Redox Biology · doi:10.1016/j.redox.2018.03.005 · Cited by 114 · see citing works
The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury
Irrera, N., Russo, M., Pallio, G., Bitto, A., Mannino, F., Minutoli, L., Altavilla, D., & Squadrito, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176204 · Cited by 97 · see citing works
Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders
Bhat, A., Ray, B., Mahalakshmi, A. M., Tuladhar, S., Nandakumar, D., Srinivasan, M., Essa, M. M., Chidambaram, S. B., Guillemin, G. J., & Sakharkar, M. K. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105078 · Cited by 107 · see citing works
From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury
Donat, C. K., Lopez, M. Y., Sastre, M., Baxan, N., Goldfinger, M., Seeamber, R., Müller, F., Davies, P., Hellyer, P. J., Siegkas, P., et al. (2020) · Brain · doi:10.1093/brain/awaa336 · Cited by 101 · see citing works
Oxidized phospholipid signaling in traumatic brain injury
Anthonymuthu, T. S., Kenny, E., Lamade, A. M., Kagan, V. E., & Bayır, H. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.031 · Cited by 99 · see citing works
Traumatic brain injury: Mechanisms, manifestations, and visual sequelae
Rauchman, S. H., Zubair, A. S., Jacob, B., Rauchman, D., Pinkhasov, A., Placantonakis, D. G., & Reiss, A. B. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1090672 · Cited by 106 · see citing works
Executive (dys)function after traumatic brain injury: special considerations for behavioral pharmacology
Ozga, J. E., Povroznik, J. M., Engler-Chiurazzi, E. B., & Haar, C. V. (2018) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000430 · Cited by 89 · see citing works
Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts
Janigro, D., Bailey, D. M., Lehmann, S., Badaut, J., O’flynn, R., Hirtz, C., & Marchi, N. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.577312 · Cited by 91 · see citing works
Systematic Review of Human and Animal Studies Examining the Efficacy and Safety of N-Acetylcysteine (NAC) and N-Acetylcysteine Amide (NACA) in Traumatic Brain Injury: Impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and Inflammation
Bhatti, J. A., Nascimento, B., Akhtar, U., Rhind, S. G., Tien, H. C. N., Nathens, A. B., & da Luz, L. T. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2017.00744 · Cited by 88 · see citing works
Reactive oxygen species-sensitive materials: A promising strategy for regulating inflammation and favoring tissue regeneration
Zhou, J., Fang, C., Rong, C., Luo, T., Liu, J., & Zhang, K. (2023) · Smart Materials in Medicine · doi:10.1016/j.smaim.2023.01.004 · Cited by 88 · see citing works
The pericyte–glia interface at the blood–brain barrier
Giannoni, P., Badaut, J., Dargazanli, C., De Maudave, A. F., Klement, W., Costalat, V., & Marchi, N. (2018) · Clinical Science · doi:10.1042/cs20171634 · Cited by 81 · see citing works
Treatment with the flavonoid 7,8-Dihydroxyflavone: a promising strategy for a constellation of body and brain disorders
Emili, M., Guidi, S., Uguagliati, B., Giacomini, A., Bartesaghi, R., & Stagni, F. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1810625 · Cited by 82 · see citing works
Traumatic Brain Injury: A Comprehensive Review of Biomechanics and Molecular Pathophysiology
Orr, T. J., Lesha, E., Kramer, A. H., Cecia, A. F., Dugan, J. E., Schwartz, B., & Einhaus, S. L. (2024) · World Neurosurgery · doi:10.1016/j.wneu.2024.01.084 · Cited by 81 · see citing works
Nanoparticle-Based Technology Approaches to the Management of Neurological Disorders
Sim, T. M., Dinesh, T., Dheen, S. T., Bay, B., & Srinivasan, D. K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176070 · Cited by 83 · see citing works
Mitochondrial dysfunctioning and neuroinflammation: Recent highlights on the possible mechanisms involved in Traumatic Brain Injury
Sahel, D. K., Kaira, M., Aran, K. R., Sharma, S., & Singh, S. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134347 · Cited by 79 · see citing works
The Kynurenine Pathway in Traumatic Brain Injury: Implications for Psychiatric Outcomes
Meier, T. B., & Savitz, J. B. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.05.021 · Cited by 77 · see citing works
Secretome of Mesenchymal Stem Cells and Its Potential Protective Effects on Brain Pathologies
Báez-Jurado, E., Hidalgo‐Lanussa, O., Barrera-Bailón, B., Sahebkar, A., Ashraf, G. M., Echeverrı́a, V., & Barreto, G. E. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1570-x · Cited by 77 · see citing works
Mitochondrial damage & lipid signaling in traumatic brain injury
Lamade, A. M., Anthonymuthu, T. S., Hier, Z. E., Gao, Y., Kagan, V. E., & Bayır, H. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113307 · Cited by 74 · see citing works
Protection by Neuroglobin Expression in Brain Pathologies
Báez-Jurado, E., Echeverrı́a, V., Cabezas, R., Ávila-Rodriguez, M., García‐Segura, L. M., & Barreto, G. E. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00146 · Cited by 70 · see citing works
Microglia Receptors in Animal Models of Traumatic Brain Injury
Younger, D., Murugan, M., Rao, K. V. R., Wu, L., & Chandra, N. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1428-7 · Cited by 69 · see citing works
Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury
Chen, X., Gao, C. H., Yan, Y., Cheng, Z., Chen, G., Rui, T., Luo, C., Gao, Y. Z., Wang, T., Chen, X., et al. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113762 · Cited by 68 · see citing works
Acute Mitochondrial Impairment Underlies Prolonged Cellular Dysfunction after Repeated Mild Traumatic Brain Injuries
Hubbard, W. B., Joseph, B., Spry, M. L., Vekaria, H. J., Saatman, K. E., & Sullivan, P. G. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5990 · Cited by 68 · see citing works
Discovery of Lipidome Alterations Following Traumatic Brain Injury via High-Resolution Metabolomics
Hogan, S., Phan, J. H., Alvarado‐Velez, M., Wang, M. D., Bellamkonda, R. V., Fernández, F. M., & LaPlaca, M. C. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00068 · Cited by 68 · see citing works
Surface-fill H2S-releasing silk fibroin hydrogel for brain repair through the repression of neuronal pyroptosis
Chen, X., Huang, X., Liu, C., Li, S., Yang, Z., Zhang, F., Chen, X., Shan, H., Tao, L., & Zhang, M. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.11.021 · Cited by 67 · see citing works
Pathophysiology of Pediatric Traumatic Brain Injury
Serpa, R. O., Ferguson, L. A., Larson, C. P., Bailard, J., Cooke, S., Greco, T., & Prins, M. L. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.696510 · Cited by 66 · see citing works
Self-citation
Deferoxamine ameliorates neurological dysfunction by inhibiting ferroptosis and neuroinflammation after traumatic brain injury
Jia, H., Liu, X., Cao, Y., Niu, H., Zhang, L., Li, R., Li, F., Sun, D., Shi, M., Wa, L., et al. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148383 · Cited by 65 · see citing works
The Bidirectional Relationship Between Sleep and Inflammation Links Traumatic Brain Injury and Alzheimer’s Disease
Green, T. R. F., Ortiz, J. B., Wonnacott, S., Williams, R. J., & Rowe, R. K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00894 · Cited by 63 · see citing works
Effects of Oral Glibenclamide on Brain Contusion Volume and Functional Outcome of Patients with Moderate and Severe Traumatic Brain Injuries: A Randomized Double-Blind Placebo-Controlled Clinical Trial.
Khalili, H., Derakhshan, N., Niakan, A., Ghaffarpasand, F., Salehi, M., Eshraghian, H., Shakibafard, A., & Zahabi, B. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.01.103 · Cited by 62 · see citing works
The ketogenic diet as a treatment for traumatic brain injury: a scoping review
McDougall, A., Bayley, M. T., & Munce, S. (2018) · Brain Injury · doi:10.1080/02699052.2018.1429025 · Cited by 63 · see citing works
Stem cells and combination therapy for the treatment of traumatic brain injury
Dekmak, A., Mantash, S., Shaito, A. A., Toutonji, A., Ramadan, N., Ghazale, H., Kassem, N. A., Darwish, H., & Zibara, K. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.12.039 · Cited by 62 · see citing works
The Complexity of Secondary Cascade Consequent to Traumatic Brain Injury: Pathobiology and Potential Treatments
Khatri, N., ‬‬‬‬‬‬‬Bommaraju, S., Kumar, S., Kaundal, R. K., Sharma, S., & Datusalia, A. K. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210215123914 · Cited by 63 · see citing works
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Authors: Prins, M., Greco, T., Alexander, D., & Giza, C. C.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Prins, Mayumi
ORCID: Prins, Mayumi
Greco, Tiffany
Giza, Christopher C.
Venue: Disease Models & Mechanisms
Publisher: The Company of Biologists
Published: 2013-01-01
Volume: 6
Issue: 6
Pages: 1307-15
ISSN: 1754-8403 (ISSN-L)
1754-8411
DOI: 10.1242/dmm.011585
PMC: PMC3820255
OpenAlex: W2141923055
Cited by: 426
References: 114
Citations by year: 2026: 7 · 2025: 29 · 2024: 37 · 2023: 40 · 2022: 41 · 2021: 55 · 2020: 55 · 2019: 40 · 2018: 46 · 2017: 27 · 2016: 14 · 2015: 24 · 2014: 8 · 2013: 3
FWCI: 10.37
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0/ (am, 3059 d)
Locations: Disease Models & Mechanisms (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of Neurological Disorders and Stroke (NS-058489, P01NS058489)
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: traumatic brain injury, pathophysiology, brain metabolism, altered mental status, injury patterns, recovery profiles, therapeutic target, TBI epidemiology
MeSH terms: Brain, Brain Injuries, Free Radicals, Glucose, Humans, Mitochondria

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