Cited by 913Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

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Clinical Trials in Head Injury

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Narayan, Raj K., Michel, Mary Ellen, Ansell, Beth, Baethmann, Alex, Biegon, Anat, Bracken, Michael B., Bullock, M. Ross, Choi, Sung C., Clifton, Guy L., Contant, Charles F., Coplin, William M., Dietrich, W. Dalton, Ghajar, Jamshid, Grady, Sean M., Grossman, Robert G., Hall, Edward D., Heetderks, William, Hovda, David A., Jallo, Jack, Katz, Russell L., Knoller, Nachshon, Kochanek, Patrick M., Maas, Andrew I., Majde, Jeannine, Marion, Donald W., Marmarou, Anthony, Marshall, Lawrence F., McIntosh, Tracy K., Miller, Emmy, Mohberg, Noel, Muizelaar, J. Paul, Pitts, Lawrence H., Quinn, Peter, Riesenfeld, Gad, Robertson, Claudia S., Strauss, Kenneth I., Teasdale, Graham, Temkin, Nancy, Tuma, Ronald, Wade, Charles, Walker, Michael D., Weinrich, Michael, Whyte, John, Wilberger, Jack, Young, A. Byron, Yurkewicz, Lorraine·2002·Journal of Neurotrauma

DOI 10.1089/089771502753754037PMC PMC1462953

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Abstract

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

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Past, Present, and Future of Traumatic Brain Injury Research
Hawryluk, G. W. J., & Bullock, M. R. (2016) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2016.05.002 · Cited by 69
“Selfotel is a competitive glutamate antagonist and was the first glutamate antagonist to go into phase III trials after an extensive preclinical evaluation process.(8,34) Magnesium acts as a noncompetitive NMDA receptor antagonist by physiologically blocking the NMDA receptor ion channel and as an intracellular calciu…”
BackgroundResultInfluentialSelf-citation
Sprouting of corticospinal tract axons from the contralateral hemisphere into the denervated side of the spinal cord is associated with functional recovery in adult rat after traumatic brain injury and erythropoietin treatment
Zhang, Y., Xiong, Y., Mahmood, A., Meng, Y., Liu, Z., Qu, C., & Chopp, M. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.046 · Cited by 56
Simultaneous monitoring of potassium, glucose and lactate during spreading depolarization in the injured human brain – Proof of principle of a novel real-time neurochemical analysis system, continuous online microdialysis
Rogers, M. L., Leong, C. L., Gowers, S. A. N., Samper, I. C., Jewell, S. L., Khan, A., McCarthy, L., Pahl, C., Tolias, C. M., Walsh, D., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16674486 · Cited by 76
Novel Therapeutic Strategies for Traumatic Brain Injury: Acute Antioxidant Reinforcement
Fernández-Gajardo, R., Matamala, J. M., Carrasco, R. A., Gutiérrez, R., Melo, R., & Rodrigo, R. (2014) · CNS Drugs · doi:10.1007/s40263-013-0138-y · Cited by 69
“have failed to display significance for their primary outcome [258–260].”
Background
Long-Term White Matter Changes after Severe Traumatic Brain Injury: A 5-Year Prospective Cohort
Dinkel, J., Drier, A., Khalilzadeh, O., Perlbarg, V., Czernecki, V., Gupta, R., Gomas, F., Sanchez-Peña, P., Dormont, D., Damien Galanaud, E., et al. (2013) · American Journal of Neuroradiology · doi:10.3174/ajnr.a3616 · Cited by 69
“TBI is biologically and clinically heterogeneous and may have a range of radiologic features.(2)”
Background
Bridge Between Neuroimmunity and Traumatic Brain Injury
Kelso, M. L., & Gendelman, H. E. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113196660653 · Cited by 57
“Notably, while immune based inflammatory responses were observed, no immune modulatory therapies have yielded a single therapeutic agent approved by the Food and Drug Administration [11, 12].”
Background
The pattern of traumatic brain injuries: A country undergoing rapid development
Bener, A., Omar, A. O. K., Ahmad, A. E., Al-mulla, F., & Rahman, Y. S. A. (2010) · Brain Injury · doi:10.3109/02699050903508192 · Cited by 62
“A US study [25] also found a similar proportion, 10% of TBIs was for severe and moderate injuries each.”
Background
Use of biomarkers for diagnosis and management of traumatic brain injury patients.
Papa, L., Robinson, G., Oli, M., Pineda, J., Demery, J. A., Brophy, G., Robicsek, S., Gabrielli, A., Robertson, C., Wang, K. K. W., et al. (2008) · Expert Opinion in Medical Diagnostics · doi:10.1517/17530059.2.8.937 · Cited by 62
“Many investigators have pointed out that the absence of biochemical markers of injury could have contributed to these failures [47,48] .”
BackgroundSelf-citation
Severe head injury and the risk of early death
Boto, G. R., Gómez, P., de la Cruz, J., & Lobato, R. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.087056 · Cited by 62
Subgroup Analysis and Covariate Adjustment in Randomized Clinical Trials of Traumatic Brain Injury: A Systematic Review
Hernández, A. V., Steyerberg, E., Taylor, G., Marmarou, A., Habbema, J., & Maas, A. (2005) · Neurosurgery · doi:10.1227/01.neu.0000186039.57548.96 · Cited by 62
“Many RCTs of acute TBI have been published, but most of these have failed to yield convincing treatment benefits (18, 32, 33, 39, 40).”
BackgroundSelf-citation
Glibenclamide Attenuates Blood–Brain Barrier Disruption in Adult Mice after Traumatic Brain Injury
Xu, Z., Yuan, F., Liu, Y.-L., Ding, J., & Tian, H.-L. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4491 · Cited by 61
Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats
Wang, B., Sun, L., Tian, Y., Li, Z., Wei, H., Wang, D., Yang, Z. R., Chen, J., Zhang, J., & Jiang, R. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.04.015 · Cited by 61
“Memory loss and learning disabilities are the most common cognitive impairments among patients with severe head injuries [29,30].”
Ghrelin Prevents Disruption of the Blood–Brain Barrier after Traumatic Brain Injury
Lopez, N., Krzyżaniak, M., Blow, C., Putnam, J., Ortiz-Pomales, Y. T., Hageny, A., Eliceiri, B. P., Coimbra, R. S. M., & Bansal, V. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.2053 · Cited by 59
“Despite the associated public health implications, there is a paucity of medical therapies for TBI (Narayan et al., 2002).”
Executive disorders and perceived socio‐emotional changes after traumatic brain injury
Rochat, L., Ammann, J., Mayer, E., Annoni, J., & der Linden, M. V. (2009) · Journal of Neuropsychology · doi:10.1348/174866408x397656 · Cited by 66
Total Intravenous Anesthesia Including Ketamine versus Volatile Gas Anesthesia for Combat-related Operative Traumatic Brain Injury
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“Although the care of these patients is complex and requires a comprehensive multidisciplinary approach, little human research has evaluated the effects of anesthesia on neurologic outcomes.(8,11)”
BackgroundMethodInfluentialSelf-citation
Recent advances in the development of multifactorial therapies for the treatment of traumatic brain injury
Vink, R., & van den Heuvel, C. (2004) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.13.10.1263 · Cited by 58
“Specifically, > 20 compounds and therapeutic interventions have been described and subjected to > 50 clinical trials in the last three decades [5-7].”
Background
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 84
“The failure of past clinical trials has been postulated to stem from poor delivery and retention of therapeutics in the brain, off-target toxicity, and a lack of understanding of the pathophysiology of TBI [93].”
Background
MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury
Jiang, Q., Qu, C., Chopp, M., Ding, G., Nejad‐Davarani, S. P., Helpern, J. A., Jensen, J. H., Zhang, Z. G., Li, L., Lü, M., et al. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1667 · Cited by 61
“2011; 24: 1119–1128 Copyright 20 primarily focused on acute therapeutic intervention to reduce cellular damage and brain edema (2); however, currently available techniques cannot repair biostructural damage to the neurons.”
Background
A Method for Reducing Misclassification in the Extended Glasgow Outcome Score
Lu, J., Marmarou, A., Lapane, K., Turf, E., & Wilson, L. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2010.1293 · Cited by 59
Self-citation
Calpain Inhibitor MDL-28170 Reduces the Functional and Structural Deterioration of Corpus Callosum following Fluid Percussion Injury
Ai, J., Liu, E., Wang, J.-L., Chen, Y.-H., Yu, J. L., & Baker, A. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.0224 · Cited by 59
“However, none has shown considerable promise (Maas, 2000, 2001; Machado et al., 1999; Narayan et al., 2002).”
Nicotinamide reduces acute cortical neuronal death and edema in the traumatically injured brain.
Hoane, M., Gilbert, D. R., Holland, M., & Pierce, J. L. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.07.011 · Cited by 59
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 64
“Early Nimodipine Calcium channel blocker [24,25]”
Background
Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury.
Hellmich, H. L., Eidson, K. A., Capra, B. A., Garcia, J. M., Boone, D. R., Hawkins, B. E., Uchida, T., Dewitt, D., & Prough, D. (2007) · Brain Research · doi:10.1016/j.brainres.2006.09.094 · Cited by 58
“5 million patients per year in the United States, causes 50,000 deaths [7,25,37] and generates an enormous economic burden in longterm disability [27,42].”
Background
Neurosurgical Treatment Variation of Traumatic Brain Injury: Evaluation of Acute Subdural Hematoma Management in Belgium and The Netherlands
van Essen, T. V., de Ruiter, G. D., Kho, K., & Peul, W. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4495 · Cited by 57
“20,21 Therefore, confronted with a patient with a traumatic ASDH, clinicians have to deal with multiple clinical and radiological variables, in a very limited time frame and with a shortage of data or predictive outcomes.”
Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using C yclosporin A as a Case Study
Margulies, S. S., Kilbaugh, T. J., Sullivan, S., Smith, C., PROPERT, K. J., Byro, M., Saliga, K., Costine, B. A., & Duhaime, A. (2015) · Brain Pathology · doi:10.1111/bpa.12247 · Cited by 59
“The heterogeneity of TBI, with distinct pathophysiologies and mechanisms associated with contusions, hemorrhages and diffuse axonal injuries, added to a panoply of variable host factors, likely contributes to the recurrent failure of large head injury treatment trials (60, 74).”
Effects of Glasgow Outcome Scale Misclassification on Traumatic Brain Injury Clinical Trials
Lu, J., Murray, G., Steyerberg, E., Butcher, I., Mchugh, G., Lingsma, H. F., Mushkudiani, N., Choi, S., Maas, A., & Marmarou, A. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2007.0510 · Cited by 57
Self-citation
Neural-respiratory inflammasome axis in traumatic brain injury
Kerr, N. A., Vaccari, J. P. D. R., Dietrich, W. D., & Keane, R. W. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113080 · Cited by 57
“These include: calcium channel blockers, corticosteroids, excitatory amino acids inhibitors, NMDA receptor antagonists, anti-inflammatory drugs, free radical scavengers, magnesium sulfate, and growth factors (20).”
BackgroundSelf-citation
Bexarotene protects against traumatic brain injury in mice partially through apolipoprotein E
Zhong, J., Cheng, C., Liu, H., Huang, Z., Wu, Y., Teng, Z., He, J., Zhang, H., Wu, J., Cao, F., et al. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.05.033 · Cited by 65
Low-Molecular-Weight Fucoidan Attenuates Mitochondrial Dysfunction and Improves Neurological Outcome After Traumatic Brain Injury in Aged Mice: Involvement of Sirt3
Wang, T., Zhu, M., & He, Z.-Z. (2016) · Cellular and molecular neurobiology · doi:10.1007/s10571-015-0323-2 · Cited by 56
Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates.
Hanrieder, J., Wetterhall, M., Enblad, P., Hillered, L., & Bergquist, J. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.10.038 · Cited by 56
Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury
Newell, E. A., Todd, B. P., Mahoney, J., Pieper, A., Ferguson, P., & Bassuk, A. (2018) · eNeuro · doi:10.1523/eneuro.0385-17.2018 · Cited by 55
Low-intensity pulsed ultrasound improves behavioral and histological outcomes after experimental traumatic brain injury
Su, W.-S., Wu, C.-H., Chen, S.-F., & Yang, F.-Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-15916-2 · Cited by 55
New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury
Neher, M. D., Weckbach, S., Huber-Lang, M. S., & Stahel, P. F. (2012) · PPAR Research · doi:10.1155/2012/728461 · Cited by 54
“Due to the promising anti-inflammatory properties of cannabinoids, a randomized phase II and III clinical trial was initiated that aimed to test HU-211 in the treatment of brain trauma [52, 61, 62].”
Background
The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway
Chen, T., Zhang, L., Qu, Y., HUO, K., Jiang, X., & Fei, Z. (2011) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2011.870 · Cited by 52
“The mGluRs are classified on the basis of amino acid sequence homologies, signal transduction pathways and pharmacological sensitivities into the following three groups: group I (mGluR1 and 5), group II (mGluR2 and 3) and group III (mGluR4, 6, 7, 8).”
Influential
The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury
Anderson, G. D., Farin, F. M., Bammler, T. K., Beyer, R. P., Swan, A. A., Wilkerson, H.-W., Kantor, E. D., & Hoane, M. R. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1911 · Cited by 49
Nicotinamide Treatment Provides Acute Neuroprotection and GFAP Regulation following Fluid Percussion Injury
Holland, M., Tan, A., Smith, D. C., & Hoane, M. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2007.0312 · Cited by 55
“Indeed, despite extensive research in the field, many of the proposed therapies that have advanced to Phase II and III clinical trials have failed to show consistent neuroprotection (Narayan et al., 2002).”
Dexamethasone attenuates early expression of three molecules associated with microglia/macrophages activation following rat traumatic brain injury
Zhang, Z.-Y., Zhang, Z.-R., Artelt, M., Burnet, M., & Schluesener, H. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0195-8 · Cited by 55
“long-term eVects with dexamethasone in TBI patients [37, 42].”
Background
Strategies for recovery and regeneration after brain and spinal cord injury
Tator, C. (2002) · Injury Prevention · doi:10.1136/ip.8.suppl_4.iv33 · Cited by 55
“32 For example, nimodipine, a calcium channel antagonist designed to reduce cerebral vasospasm by reducing intra-cellular calcium, improves the recovery from brain injury in patients with accompanying traumatic subarachnoid hemorrhage.”
Background
The Increasing Age of TBI Patients at a Single Level 1 Trauma Center and the Discordance Between GCS and CT Rotterdam Scores in the Elderly
Garza, N., Toussi, A., Wilson, M. D., Shahlaie, K., & Martin, R. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00112 · Cited by 54
“Number of patients (% total) 3,179 (100) 885 (28) 549 (17) 785 (25) 960 (30)”
Method
Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits Induced by Experimental Traumatic Brain Injury
Casili, G., Campolo, M., Paterniti, I., Lanza, M., Filippone, A., Cuzzocrea, S., & Esposito, E. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5260 · Cited by 54
“39 Among the factors leading to TBI outcome, there are biochemical mechanisms generating oxidative stress.”
Traumatic Brain Injury
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The Novel Apolipoprotein E–Based Peptide COG1410 Improves Sensorimotor Performance and Reduces Injury Magnitude following Cortical Contusion Injury
Hoane, M. R., Pierce, J. L., Holland, M. A., Birky, N. D., Dang, T., Vitek, M. P., & McKenna, S. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.0254 · Cited by 50
“This major health issue is compounded by the limited number of pharmacological treatments that are currently available for patients suffering head injuries, which is surprising because of the amount of effort invested into finding such treatments (Statler et al., 2001; Narayan et al., 2002).”
Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?
Vauzour, D., Martinsen, A., & Layé, S. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.08.004 · Cited by 60
Traumatic Brain Injury and Aging: Is a Combination of Progesterone and Vitamin D Hormone a Simple Solution to a Complex Problem?
Cekic, M. M., & Stein, D. G. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2009.10.017 · Cited by 43
“At least in part because of this complexity, most drugs designed as monotherapies to modulate single receptors or related groups of mechanisms have failed in clinical trials for TBI, despite showing preclinical promise.(5,6) In addition to the complexity inherent in the injury process itself, the systemic and extraneu…”
Impact of Early Pharmacological Treatment on Cognitive and Behavioral Outcome After Traumatic Brain Injury in Adults: A Meta-Analysis
Wheaton, P., Mathias, J., & Vink, R. (2009) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181b66f04 · Cited by 53

Authors: Narayan, R. K., Michel, M. E., Ansell, B., Baethmann, A., Biegon, A., Bracken, M. B., Bullock, M. R., Choi, S. C., Clifton, G. L., Contant, C. F., Coplin, W. M., Dietrich, W. D., Ghajar, J., Grady, S. M., Grossman, R. G., Hall, E. D., Heetderks, W., Hovda, D. A., Jallo, J., Katz, R. L., Knoller, N., Kochanek, P. M., Maas, A. I., Majde, J., Marion, D. W., Marmarou, A., Marshall, L. F., McIntosh, T. K., Miller, E., Mohberg, N., Muizelaar, J. P., Pitts, L. H., Quinn, P., Riesenfeld, G., Robertson, C. S., Strauss, K. I., Teasdale, G., Temkin, N., Tuma, R., Wade, C., Walker, M. D., Weinrich, M., Whyte, J., Wilberger, J., Young, A. B., & Yurkewicz, L.
Affiliations: Temple University Hospital (US)
National Institute of Neurological Disorders and Stroke (US)
National Institutes of Health (US)
Ludwig-Maximilians-Universität München (DE)
Lawrence Berkeley National Laboratory (US)
Yale University (US)
Virginia Commonwealth University (US)
The University of Texas Health Science Center at Houston (US)
Baylor College of Medicine (US)
Wayne State University (US)
University of Miami (US)
Brain Trauma Foundation (US)
Hospital of the University of Pennsylvania (US)
Pfizer (United States) (US)
University of California, Los Angeles (US)
Temple University (US)
United States Food and Drug Administration (US)
Sheba Medical Center (IL)
University of Pittsburgh (US)
Academisch Ziekenhuis Rotterdam (NL)
Office of Naval Research (US)
University of California San Diego (US)
University of California Davis Medical Center (US)
University of California, San Francisco (US)
Southern General Hospital (GB)
University of Washington (US)
Allegheny General Hospital (US)
Albert B. Chandler Hospital (US)
ORCID: Narayan, Raj K.
Biegon, Anat
Choi, Sung C.
Dietrich, W. Dalton
Grady, Sean M.
Grossman, Robert G.
Heetderks, William
Jallo, Jack
Kochanek, Patrick M.
Maas, Andrew I.
Marion, Donald W.
McIntosh, Tracy K.
Robertson, Claudia S.
Temkin, Nancy
Wade, Charles
Walker, Michael D.
Weinrich, Michael
Whyte, John
Venue: Journal of Neurotrauma
Publisher: SAGE Publications
Published: 2002-05
Volume: 19
Issue: 5
Pages: 503-557
ISSN: 0897-7151 (ISSN-L)
1557-9042
DOI: 10.1089/089771502753754037
PMC: PMC1462953
OpenAlex: W2045663952
Cited by: 913
References: 0
Citations by year: 2026: 11 · 2025: 16 · 2024: 20 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 35 · 2019: 43 · 2018: 43 · 2017: 40 · 2016: 42 · 2015: 55 · 2014: 49 · 2013: 56 · 2012: 61
FWCI: 20.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Journal of Neurotrauma (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
PubMed Central (acceptedVersion)
Deep Blue (University of Michigan) (submittedVersion, public-domain)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders: National Institutes of Health (7r01ns038654-04)
National Institute of Neurological Disorders and Stroke (R01-NS038654)
Topics: Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
Keywords: traumatic brain injury, clinical trial design, closed head injury, penetrating head injury, translational research, treatment failure, long-term disability
MeSH terms: Brain Injuries, Clinical Trials as Topic, Humans

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