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Samuel S. Shin, C. Edward Dixon, David O. Okonkwo and R. Mark Richardson

T here are multiple therapy modalities for attenuating neurological disabilities in traumatic brain injury (TBI) patients, including occupational, physical, and cognitive rehabilitation, but there is a critical need for more effective therapies, especially pharmacological or surgical treatments. The pathophysiology of TBI is complex and includes inflammation, oxidative stress, apoptosis, excitotoxicity, and mitochondrial dysfunction. After almost a century of translational science, there has yet to be a successful Phase III clinical trial investigating a

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Matthew T. Harting, James E. Baumgartner, Laura L. Worth, Linda Ewing-Cobbs, Adrian P. Gee, Mary-Clare Day and Charles S. Cox Jr.

T raumatic brain injury directly affects an estimated 1.5 million Americans annually, although the resultant acute and/or chronic deficits in motor, cognitive, behavioral, and/or social functioning have equally devastating effects on friends, families, and society. 2 Of the TBIs suffered each year, ~50,000 deaths result, and nearly 100,000 injuries lead to life-long impairment with substantial loss of function. 2 Traumatic brain injury contributes to 50% of all trauma-related deaths. 25 The national economic impact is difficult to quantify, due to the

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Alexandra D. Beier and Peter B. Dirks

: 508 – 510 , 2000 5 Hashimoto T , Nakamura N , Richard KE , Frowein RA : Primary brain stem lesions caused by closed head injuries . Neurosurg Rev 16 : 291 – 298 , 1993 6 Jacob AT , Heuer GG , Grant R , Georgoff P , Danish SF , Storm PB , : Decompressive hemicraniectomy for pediatric traumatic brain injury: long-term outcome based on quality of life . Pediatr Neurosurg 47 : 81 – 86 , 2011 7 Jagannathan J , Okonkwo DO , Dumont AS , Ahmed H , Bahari A , Prevedello DM , : Outcome following decompressive

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Shirley I. Stiver and Geoffrey T. Manley

: Fluid replacement for hypotensive injury victims: how, when and what risks? . Curr Opin Anaesthesiol 11 : 177 – 180 , 1998 13 Bloch M : Cerebral effects of rewarming following prolonged hypothermia: significance for the management of severe cranio-cerebral injury and acute pyrexia . Brain 90 : 769 – 784 , 1967 14 Bochicchio GV , Ilahi O , Joshi M , Bochicchio K , Scalea TM : Endotracheal intubation in the field does not improve outcome in trauma patients who present without an acutely lethal traumatic brain injury . J Trauma 54 : 307

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Leonardo Rangel-Castilla, Jaime Gasco, Haring J. W. Nauta, DaviD O. Okonkwo and Claudia S. Robertson

, Stringer WA , Choi SC , Fatouros P , Young HF : Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography . J Neurosurg 77 : 360 – 368 , 1992 6 Bratton SL , Chestnut RM , Ghajar J , McConnell Hammond FF , Harris OA , Hartl R , : Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy . J Neurotrauma 24 : 1 Suppl S14 – S20 , 2007 7 Bratton SL , Chestnut RM , Ghajar J , McConnell Hammond FF , Harris OA

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Adam Ross Befeler, William Gordon, Nickalus Khan, Julius Fernandez, Michael Scott Muhlbauer and Jeffrey Marius Sorenson

management of traumatic brain injury? A prospective evaluation . J Trauma 57 : 939 – 943 , 2004 5 Brown CV , Zada G , Salim A , Inaba K , Kasotakis G , Hadjizacharia P , : Indications for routine repeat head computed tomography (CT) stratified by severity of traumatic brain injury . J Trauma 62 : 1339 – 1345 , 2007 6 Chao A , Pearl J , Perdue P , Wang D , Bridgeman A , Kennedy S , : Utility of routine serial computed tomography for blunt intracranial injury . J Trauma 51 : 870 – 876 , 2001 7 Fazel R , Krumholz HM

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Efthimios Dardiotis, Kostas N. Fountas, Maria Dardioti, Georgia Xiromerisiou, Eftychia Kapsalaki, Anastasia Tasiou and Georgios M. Hadjigeorgiou

elevated, and this upregulation after injury was associated with better neurological outcome. 18 However, a polymorphism in the promoter of IL-6 was not found to have any effect on the outcome of patients with TBI. 88 Other Association Studies Clinical studies in patients who have sustained TBI have investigated the role of genetic variants in genes that modulate neurotransmitters such as dopamine 81 or serotonin. 16 Traumatic brain injury induces excessive neurotransmitter release, and this may affect motor function, behavior, mood, and cognition. Dopamine

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Ryan S. Kitagawa, Robert M. Van Haren, Shoji Yokobori, David Cohen, Samuel R. Beckerman, Faiz Ahmad and M. Ross Bullock

LE : Traumatic aortic injury: computerized tomographic findings at presentation and after conservative therapy . J Comput Assist Tomogr 34 : 388 – 394 , 2010 2 Andrews PJ , Sleeman DH , Statham PF , McQuatt A , Corruble V , Jones PA , : Predicting recovery in patients suffering from traumatic brain injury by using admission variables and physiological data: a comparison between decision tree analysis and logistic regression . J Neurosurg 97 : 326 – 336 , 2002 3 Arthurs ZM , Starnes BW , Sohn VY , Singh N , Martin MJ

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Bon H. Verweij, J. Paul Muizelaar, Federico C. Vinas, Patti L. Peterson, Ye Xiong and Chuan P. Lee

–497, 1982 2. Bergsneider M , Hovda DA , Shalmon E , et al : Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86 : 241 – 251 , 1997 Bergsneider M, Hovda DA, Shalmon E, et al: Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86: 241–251, 1997 3. Berman RF , Verweij BH , Muizelaar JP : Neurobehavioral protection by the neuronal calcium channel blocker Ziconotide in a model of traumatic diffuse brain

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Je Yeong Sone, Douglas Kondziolka, Jason H. Huang and Uzma Samadani

T he most prevalent method of preventing or minimizing traumatic brain injury (TBI) is helmet use. Helmets are one of the earliest and most enduring methods of personal protection in the history of human civilization. They provide protection from head trauma by absorbing the impact energy and diffusing and displacing peak impact and pressure gradient to a greater surface area of the head, rather than to a localized region. 76 History of Pre-20th–Century Helmets Since the helmet's inception, the vast majority have been designed for ceremonial uses and