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Published in: CNS Drugs 9/2016

01-09-2016 | Systematic Review

Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature

Authors: Shaun E. Gruenbaum, Alexander Zlotnik, Benjamin F. Gruenbaum, Denise Hersey, Federico Bilotta

Published in: CNS Drugs | Issue 9/2016

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Abstract

Introduction

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The deleterious effects of secondary brain injury may be attenuated by early pharmacological therapy in the emergency room and intensive care unit (ICU). Current medical management of acute TBI is primarily supportive, aimed at reducing intracranial pressure (ICP) and optimizing cerebral perfusion. There are no pharmacological therapies to date that have been unequivocally demonstrated to improve neurological outcomes after TBI.

Objectives

The purpose of this systematic review was to evaluate the recent clinical studies from January 2013 through November 2015 that investigated neuroprotective functional outcomes of pharmacological agents after TBI.

Methods

The following databases were searched for relevant studies: MEDLINE (OvidSP January Week 1, 2013–November Week 2 2015), Embase (OvidSP 2013 January 1–2015 November 24), and the unindexed material in PubMed (National Library of Medicine/National Institutes of Health [NLM/NIH]). This systematic review included only full-length clinical studies and case series that included at least five patients and were published in the English language. Only studies that examined functional clinical outcomes were included.

Results

Twenty-five of 527 studies met our inclusion criteria, which investigated 15 independent pharmacological therapies. Eight of these therapies demonstrated possible neuroprotective properties and improved functional outcomes, of which five were investigated with randomized clinical trials: statins, N-acetyl cysteine (NAC), Enzogenol, Cerebrolysin, and nitric oxide synthase inhibitor (VAS203). Three pharmacological agents did not demonstrate neuroprotective effects, and four agents had mixed results.

Conclusions

While there is currently no single pharmacological therapy that will unequivocally improve clinical outcomes after TBI, several agents have demonstrated promising clinical benefits for specific TBI patients and should be investigated further.
Appendix
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Literature
1.
go back to reference Kirkpatrick AW, Ball CG, D’Amours SK, Zygun D. Acute resuscitation of the unstable adult trauma patient: bedside diagnosis and therapy. Can J Surg. 2008;51(1):57–69.PubMedPubMedCentral Kirkpatrick AW, Ball CG, D’Amours SK, Zygun D. Acute resuscitation of the unstable adult trauma patient: bedside diagnosis and therapy. Can J Surg. 2008;51(1):57–69.PubMedPubMedCentral
2.
go back to reference Lu C, Xia J, Bin W, Wu Y, Liu X, Zhang Y. Advances in diagnosis, treatments, and molecular mechanistic studies of traumatic brain injury. Biosci Trends. 2015;9(3):138–48.PubMedCrossRef Lu C, Xia J, Bin W, Wu Y, Liu X, Zhang Y. Advances in diagnosis, treatments, and molecular mechanistic studies of traumatic brain injury. Biosci Trends. 2015;9(3):138–48.PubMedCrossRef
3.
go back to reference Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4.PubMedCrossRef Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4.PubMedCrossRef
4.
go back to reference Gerber LM, Chiu YL, Carney N, Hartl R, Ghajar J. Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg. 2013;119(6):1583–90.PubMedCrossRef Gerber LM, Chiu YL, Carney N, Hartl R, Ghajar J. Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg. 2013;119(6):1583–90.PubMedCrossRef
5.
go back to reference Marmarou A, Lu J, Butcher I, McHugh GS, Mushkudiani NA, Murray GD, et al. IMPACT database of traumatic brain injury: design and description. J Neurotrauma. 2007;24(2):239–50.PubMedCrossRef Marmarou A, Lu J, Butcher I, McHugh GS, Mushkudiani NA, Murray GD, et al. IMPACT database of traumatic brain injury: design and description. J Neurotrauma. 2007;24(2):239–50.PubMedCrossRef
6.
go back to reference Levin HS, Saydjari C, Eisenberg HM, Foulkes M, Marshall LF, Ruff RM, et al. Vegetative state after closed-head injury. A Traumatic Coma Data Bank report. Arch Neurol. 1991;48(6):580–5.PubMedCrossRef Levin HS, Saydjari C, Eisenberg HM, Foulkes M, Marshall LF, Ruff RM, et al. Vegetative state after closed-head injury. A Traumatic Coma Data Bank report. Arch Neurol. 1991;48(6):580–5.PubMedCrossRef
7.
go back to reference Murray LS, Teasdale GM, Murray GD, Miller DJ, Pickard JD, Shaw MD. Head injuries in four British neurosurgical centres. Br J Neurosurg. 1999;13(6):564–9.PubMedCrossRef Murray LS, Teasdale GM, Murray GD, Miller DJ, Pickard JD, Shaw MD. Head injuries in four British neurosurgical centres. Br J Neurosurg. 1999;13(6):564–9.PubMedCrossRef
8.
go back to reference Murray GD, Teasdale GM, Braakman R, Cohadon F, Dearden M, Iannotti F, et al. The European Brain Injury Consortium survey of head injuries. Acta Neurochir. 1999;141(3):223–36.PubMedCrossRef Murray GD, Teasdale GM, Braakman R, Cohadon F, Dearden M, Iannotti F, et al. The European Brain Injury Consortium survey of head injuries. Acta Neurochir. 1999;141(3):223–36.PubMedCrossRef
9.
go back to reference Stocchetti N, Paterno R, Citerio G, Beretta L, Colombo A. Traumatic brain injury in an aging population. J Neurotrauma. 2012;29(6):1119–25.PubMedCrossRef Stocchetti N, Paterno R, Citerio G, Beretta L, Colombo A. Traumatic brain injury in an aging population. J Neurotrauma. 2012;29(6):1119–25.PubMedCrossRef
10.
go back to reference Myburgh JA, Cooper DJ, Finfer SR, Venkatesh B, Jones D, Higgins A, et al. Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand. J Trauma. 2008;64(4):854–62.PubMedCrossRef Myburgh JA, Cooper DJ, Finfer SR, Venkatesh B, Jones D, Higgins A, et al. Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand. J Trauma. 2008;64(4):854–62.PubMedCrossRef
11.
go back to reference Muehlschlegel S, Carandang R, Ouillette C, Hall W, Anderson F, Goldberg R. Frequency and impact of intensive care unit complications on moderate-severe traumatic brain injury: early results of the Outcome Prognostication in Traumatic Brain Injury (OPTIMISM) Study. Neurocrit Care. 2013;18(3):318–31.PubMedCrossRef Muehlschlegel S, Carandang R, Ouillette C, Hall W, Anderson F, Goldberg R. Frequency and impact of intensive care unit complications on moderate-severe traumatic brain injury: early results of the Outcome Prognostication in Traumatic Brain Injury (OPTIMISM) Study. Neurocrit Care. 2013;18(3):318–31.PubMedCrossRef
12.
go back to reference McConeghy KW, Hatton J, Hughes L, Cook AM. A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury. CNS Drugs. 2012;26(7):613–36.PubMedCrossRef McConeghy KW, Hatton J, Hughes L, Cook AM. A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury. CNS Drugs. 2012;26(7):613–36.PubMedCrossRef
13.
go back to reference Falleti MG, Maruff P, Burman P, Harris A. The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature. Psychoneuroendocrinology. 2006;31(6):681–91.PubMedCrossRef Falleti MG, Maruff P, Burman P, Harris A. The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature. Psychoneuroendocrinology. 2006;31(6):681–91.PubMedCrossRef
14.
go back to reference Agha A, Rogers B, Sherlock M, O’Kelly P, Tormey W, Phillips J, et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab. 2004;89(10):4929–36.PubMedCrossRef Agha A, Rogers B, Sherlock M, O’Kelly P, Tormey W, Phillips J, et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab. 2004;89(10):4929–36.PubMedCrossRef
15.
go back to reference Prodam F, Pagano L, Corneli G, Golisano G, Belcastro S, Busti A, et al. Update on epidemiology, etiology, and diagnosis of adult growth hormone deficiency. J Endocrinol Invest. 2008;31(9 Suppl):6–11.PubMed Prodam F, Pagano L, Corneli G, Golisano G, Belcastro S, Busti A, et al. Update on epidemiology, etiology, and diagnosis of adult growth hormone deficiency. J Endocrinol Invest. 2008;31(9 Suppl):6–11.PubMed
16.
go back to reference Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M. Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma. 2013;30(11):998–1006.PubMedCrossRef Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M. Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma. 2013;30(11):998–1006.PubMedCrossRef
17.
go back to reference Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Horm Behav. 2013;63(2):331–44.PubMedCrossRef Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Horm Behav. 2013;63(2):331–44.PubMedCrossRef
18.
go back to reference Gardner CJ, Mattsson AF, Daousi C, Korbonits M, Koltowska-Haggstrom M, Cuthbertson DJ. GH deficiency after traumatic brain injury: improvement in quality of life with GH therapy: analysis of the KIMS database. Eur J Endocrinol. 2015;172(4):371–81.PubMedCrossRef Gardner CJ, Mattsson AF, Daousi C, Korbonits M, Koltowska-Haggstrom M, Cuthbertson DJ. GH deficiency after traumatic brain injury: improvement in quality of life with GH therapy: analysis of the KIMS database. Eur J Endocrinol. 2015;172(4):371–81.PubMedCrossRef
19.
go back to reference Mahmood A, Goussev A, Kazmi H, Qu C, Lu D, Chopp M. Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Neurosurgery. 2009;65(1):187–91 (discussion 91-2).PubMedPubMedCentralCrossRef Mahmood A, Goussev A, Kazmi H, Qu C, Lu D, Chopp M. Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Neurosurgery. 2009;65(1):187–91 (discussion 91-2).PubMedPubMedCentralCrossRef
20.
go back to reference Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, et al. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma. 2004;21(1):21–32.PubMedCrossRef Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, et al. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma. 2004;21(1):21–32.PubMedCrossRef
21.
go back to reference Sanchez-Aguilar M, Tapia-Perez JH, Sanchez-Rodriguez JJ, Vinas-Rios JM, Martinez-Perez P, de la Cruz-Mendoza E, et al. Effect of rosuvastatin on cytokines after traumatic head injury. J Neurosurg. 2013;118(3):669–75.PubMedCrossRef Sanchez-Aguilar M, Tapia-Perez JH, Sanchez-Rodriguez JJ, Vinas-Rios JM, Martinez-Perez P, de la Cruz-Mendoza E, et al. Effect of rosuvastatin on cytokines after traumatic head injury. J Neurosurg. 2013;118(3):669–75.PubMedCrossRef
22.
go back to reference Orlando A, Bar-Or D, Salottolo K, Levy AS, Mains CW, Slone DS, et al. Unintentional discontinuation of statins may increase mortality after traumatic brain injury in elderly patients: a preliminary observation. J Clin Med Res. 2013;5(3):168–73.PubMedPubMedCentral Orlando A, Bar-Or D, Salottolo K, Levy AS, Mains CW, Slone DS, et al. Unintentional discontinuation of statins may increase mortality after traumatic brain injury in elderly patients: a preliminary observation. J Clin Med Res. 2013;5(3):168–73.PubMedPubMedCentral
23.
go back to reference Yoles E, Belkin M, Schwartz M. HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy. J Neurotrauma. 1996;13(1):49–57.PubMedCrossRef Yoles E, Belkin M, Schwartz M. HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy. J Neurotrauma. 1996;13(1):49–57.PubMedCrossRef
24.
go back to reference Shohami E, Biegon A. Novel approach to the role of NMDA receptors in traumatic brain injury. CNS Neurol Disord Drug Targets. 2014;13(4):567–73.PubMedCrossRef Shohami E, Biegon A. Novel approach to the role of NMDA receptors in traumatic brain injury. CNS Neurol Disord Drug Targets. 2014;13(4):567–73.PubMedCrossRef
25.
go back to reference Brewster ME, Pop E, Foltz RL, Reuschel S, Griffith W, Amselem S, et al. Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU-211), a neuroprotectant agent, in normal volunteers. Int J Clin Pharmacol Ther. 1997;35(9):361–5.PubMed Brewster ME, Pop E, Foltz RL, Reuschel S, Griffith W, Amselem S, et al. Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU-211), a neuroprotectant agent, in normal volunteers. Int J Clin Pharmacol Ther. 1997;35(9):361–5.PubMed
26.
go back to reference Knoller N, Levi L, Shoshan I, Reichenthal E, Razon N, Rappaport ZH, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med. 2002;30(3):548–54.PubMedCrossRef Knoller N, Levi L, Shoshan I, Reichenthal E, Razon N, Rappaport ZH, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med. 2002;30(3):548–54.PubMedCrossRef
27.
go back to reference Maas AI, Murray G, Henney H 3rd, Kassem N, Legrand V, Mangelus M, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol. 2006;5(1):38–45.PubMedCrossRef Maas AI, Murray G, Henney H 3rd, Kassem N, Legrand V, Mangelus M, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol. 2006;5(1):38–45.PubMedCrossRef
28.
go back to reference Nguyen BM, Kim D, Bricker S, Bongard F, Neville A, Putnam B, et al. Effect of marijuana use on outcomes in traumatic brain injury. Am Surg. 2014;80(10):979–83.PubMed Nguyen BM, Kim D, Bricker S, Bongard F, Neville A, Putnam B, et al. Effect of marijuana use on outcomes in traumatic brain injury. Am Surg. 2014;80(10):979–83.PubMed
29.
go back to reference Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981;8(1):10–4.PubMedCrossRef Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981;8(1):10–4.PubMedCrossRef
30.
go back to reference Arbabi S, Campion EM, Hemmila MR, Barker M, Dimo M, Ahrns KS, et al. Beta-blocker use is associated with improved outcomes in adult trauma patients. J Trauma. 2007;62(1):56–61 (discussion 61–2).PubMedCrossRef Arbabi S, Campion EM, Hemmila MR, Barker M, Dimo M, Ahrns KS, et al. Beta-blocker use is associated with improved outcomes in adult trauma patients. J Trauma. 2007;62(1):56–61 (discussion 61–2).PubMedCrossRef
31.
go back to reference Mohseni S, Talving P, Wallin G, Ljungqvist O, Riddez L. Preinjury beta-blockade is protective in isolated severe traumatic brain injury. J Trauma Acute Care Surg. 2014;76(3):804–8.PubMedCrossRef Mohseni S, Talving P, Wallin G, Ljungqvist O, Riddez L. Preinjury beta-blockade is protective in isolated severe traumatic brain injury. J Trauma Acute Care Surg. 2014;76(3):804–8.PubMedCrossRef
32.
go back to reference Sekhon B, Sekhon C, Khan M, Patel SJ, Singh I, Singh AK. N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia. Brain Res. 2003;971(1):1–8.PubMedCrossRef Sekhon B, Sekhon C, Khan M, Patel SJ, Singh I, Singh AK. N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia. Brain Res. 2003;971(1):1–8.PubMedCrossRef
33.
go back to reference Hicdonmez T, Kanter M, Tiryaki M, Parsak T, Cobanoglu S. Neuroprotective effects of N-acetylcysteine on experimental closed head trauma in rats. Neurochem Res. 2006;31(4):473–81.PubMedCrossRef Hicdonmez T, Kanter M, Tiryaki M, Parsak T, Cobanoglu S. Neuroprotective effects of N-acetylcysteine on experimental closed head trauma in rats. Neurochem Res. 2006;31(4):473–81.PubMedCrossRef
34.
go back to reference Hoffer ME, Balaban C, Slade MD, Tsao JW, Hoffer B. Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled study. PloS One. 2013;8(1):e54163.PubMedPubMedCentralCrossRef Hoffer ME, Balaban C, Slade MD, Tsao JW, Hoffer B. Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled study. PloS One. 2013;8(1):e54163.PubMedPubMedCentralCrossRef
35.
go back to reference Shand B, Strey C, Scott R, Morrison Z, Gieseg S. Pilot study on the clinical effects of dietary supplementation with Enzogenol, a flavonoid extract of pine bark and vitamin C. Phytother Res. 2003;17(5):490–4.PubMedCrossRef Shand B, Strey C, Scott R, Morrison Z, Gieseg S. Pilot study on the clinical effects of dietary supplementation with Enzogenol, a flavonoid extract of pine bark and vitamin C. Phytother Res. 2003;17(5):490–4.PubMedCrossRef
36.
go back to reference Theadom A, Mahon S, Barker-Collo S, McPherson K, Rush E, Vandal AC, et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol. 2013;20(8):1135–44.PubMedCrossRef Theadom A, Mahon S, Barker-Collo S, McPherson K, Rush E, Vandal AC, et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol. 2013;20(8):1135–44.PubMedCrossRef
37.
go back to reference Masliah E, Diez-Tejedor E. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs Today (Barc). 2012;48(Suppl A):3–24. Masliah E, Diez-Tejedor E. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs Today (Barc). 2012;48(Suppl A):3–24.
38.
go back to reference Chen CC, Wei ST, Tsaia SC, Chen XX, Cho DY. Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study. Br J Neurosurg. 2013;27(6):803–7.PubMedCrossRef Chen CC, Wei ST, Tsaia SC, Chen XX, Cho DY. Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study. Br J Neurosurg. 2013;27(6):803–7.PubMedCrossRef
39.
go back to reference Guzik TJ, West NE, Pillai R, Taggart DP, Channon KM. Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension. 2002;39(6):1088–94.PubMedCrossRef Guzik TJ, West NE, Pillai R, Taggart DP, Channon KM. Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension. 2002;39(6):1088–94.PubMedCrossRef
40.
go back to reference Terpolilli NA, Zweckberger K, Trabold R, Schilling L, Schinzel R, Tegtmeier F, et al. The novel nitric oxide synthase inhibitor 4-amino-tetrahydro-L-biopterine prevents brain edema formation and intracranial hypertension following traumatic brain injury in mice. J Neurotrauma. 2009;26(11):1963–75.PubMedCrossRef Terpolilli NA, Zweckberger K, Trabold R, Schilling L, Schinzel R, Tegtmeier F, et al. The novel nitric oxide synthase inhibitor 4-amino-tetrahydro-L-biopterine prevents brain edema formation and intracranial hypertension following traumatic brain injury in mice. J Neurotrauma. 2009;26(11):1963–75.PubMedCrossRef
41.
go back to reference Stover JF, Belli A, Boret H, Bulters D, Sahuquillo J, Schmutzhard E, et al. Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized phase IIa trial (NOSTRA). J Neurotrauma. 2014;31(19):1599–606.PubMedCrossRef Stover JF, Belli A, Boret H, Bulters D, Sahuquillo J, Schmutzhard E, et al. Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized phase IIa trial (NOSTRA). J Neurotrauma. 2014;31(19):1599–606.PubMedCrossRef
42.
go back to reference Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, et al. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke. 2007;38(9):2526–30.PubMedPubMedCentralCrossRef Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, et al. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke. 2007;38(9):2526–30.PubMedPubMedCentralCrossRef
43.
go back to reference Zweckberger K, Hackenberg K, Jung CS, Hertle DN, Kiening KL, Unterberg AW, et al. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury. Neuroscience. 2014;272:199–206.PubMedCrossRef Zweckberger K, Hackenberg K, Jung CS, Hertle DN, Kiening KL, Unterberg AW, et al. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury. Neuroscience. 2014;272:199–206.PubMedCrossRef
44.
go back to reference Patel AD, Gerzanich V, Geng Z, Simard JM. Glibenclamide reduces hippocampal injury and preserves rapid spatial learning in a model of traumatic brain injury. J Neuropathol Exp Neurol. 2010;69(12):1177–90.PubMedCrossRef Patel AD, Gerzanich V, Geng Z, Simard JM. Glibenclamide reduces hippocampal injury and preserves rapid spatial learning in a model of traumatic brain injury. J Neuropathol Exp Neurol. 2010;69(12):1177–90.PubMedCrossRef
45.
go back to reference Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V. Sulfonylurea receptor 1 in central nervous system injury: a focused review. J Cereb Blood Flow Metab. 2012;32(9):1699–717.PubMedPubMedCentralCrossRef Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V. Sulfonylurea receptor 1 in central nervous system injury: a focused review. J Cereb Blood Flow Metab. 2012;32(9):1699–717.PubMedPubMedCentralCrossRef
46.
go back to reference Ding J, Yuan F, Guo JY, Chen H, Tian HL. Influence of glibenclamide on outcome in patients with type 2 diabetes and traumatic brain injury. Clin Neurlo Neurosurg. 2013;115(10):2166–9.CrossRef Ding J, Yuan F, Guo JY, Chen H, Tian HL. Influence of glibenclamide on outcome in patients with type 2 diabetes and traumatic brain injury. Clin Neurlo Neurosurg. 2013;115(10):2166–9.CrossRef
47.
go back to reference Aminmansour B, Fard SA, Habibabadi MR, Moein P, Norouzi R, Naderan M. The efficacy of cyclosporine-a on diffuse axonal injury after traumatic brain injury. Adv Biomed Res. 2014;3:35.PubMedPubMedCentralCrossRef Aminmansour B, Fard SA, Habibabadi MR, Moein P, Norouzi R, Naderan M. The efficacy of cyclosporine-a on diffuse axonal injury after traumatic brain injury. Adv Biomed Res. 2014;3:35.PubMedPubMedCentralCrossRef
48.
go back to reference Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24.PubMedCrossRef Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24.PubMedCrossRef
49.
go back to reference Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990;323(8):497–502.PubMedCrossRef Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990;323(8):497–502.PubMedCrossRef
50.
go back to reference Rowe AS, Goodwin H, Brophy GM, Bushwitz J, Castle A, Deen D, et al. Seizure prophylaxis in neurocritical care: a review of evidence-based support. Pharmacotherapy. 2014;34(4):396–409.PubMedCrossRef Rowe AS, Goodwin H, Brophy GM, Bushwitz J, Castle A, Deen D, et al. Seizure prophylaxis in neurocritical care: a review of evidence-based support. Pharmacotherapy. 2014;34(4):396–409.PubMedCrossRef
51.
go back to reference Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12(2):165–72.PubMedCrossRef Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12(2):165–72.PubMedCrossRef
52.
go back to reference Taylor S, Heinrichs RJ, Janzen JM, Ehtisham A. Levetiracetam is associated with improved cognitive outcome for patients with intracranial hemorrhage. Neurocrit Care. 2011;15(1):80–4.PubMedCrossRef Taylor S, Heinrichs RJ, Janzen JM, Ehtisham A. Levetiracetam is associated with improved cognitive outcome for patients with intracranial hemorrhage. Neurocrit Care. 2011;15(1):80–4.PubMedCrossRef
53.
go back to reference Wang H, Gao J, Lassiter TF, McDonagh DL, Sheng H, Warner DS, et al. Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. Neurocrit Care. 2006;5(1):71–8.PubMedCrossRef Wang H, Gao J, Lassiter TF, McDonagh DL, Sheng H, Warner DS, et al. Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. Neurocrit Care. 2006;5(1):71–8.PubMedCrossRef
54.
go back to reference Chen HI, Malhotra NR, Oddo M, Heuer GG, Levine JM, LeRoux PD. Barbiturate infusion for intractable intracranial hypertension and its effect on brain oxygenation. Neurosurgery. 2008;63(5):880–6 (discussion 6–7).PubMedCrossRef Chen HI, Malhotra NR, Oddo M, Heuer GG, Levine JM, LeRoux PD. Barbiturate infusion for intractable intracranial hypertension and its effect on brain oxygenation. Neurosurgery. 2008;63(5):880–6 (discussion 6–7).PubMedCrossRef
55.
go back to reference Gabriel WM, Rowe AS. Long-term comparison of GOS-E scores in patients treated with phenytoin or levetiracetam for posttraumatic seizure prophylaxis after traumatic brain injury. Ann Pharmacother. 2014;48(11):1440–4.PubMedCrossRef Gabriel WM, Rowe AS. Long-term comparison of GOS-E scores in patients treated with phenytoin or levetiracetam for posttraumatic seizure prophylaxis after traumatic brain injury. Ann Pharmacother. 2014;48(11):1440–4.PubMedCrossRef
56.
go back to reference Deutsch ER, Espinoza TR, Atif F, Woodall E, Kaylor J, Wright DW. Progesterone’s role in neuroprotection, a review of the evidence. Brain Res. 2013;1530:82–105.PubMedCrossRef Deutsch ER, Espinoza TR, Atif F, Woodall E, Kaylor J, Wright DW. Progesterone’s role in neuroprotection, a review of the evidence. Brain Res. 2013;1530:82–105.PubMedCrossRef
57.
go back to reference Wei J, Xiao GM. The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects. Acta Pharmacol Sin. 2013;34(12):1485–90.PubMedPubMedCentralCrossRef Wei J, Xiao GM. The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects. Acta Pharmacol Sin. 2013;34(12):1485–90.PubMedPubMedCentralCrossRef
58.
go back to reference Shakeri M, Boustani MR, Pak N, Panahi F, Salehpour F, Lotfinia I, et al. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Clin Neurol Neurosurg. 2013;115(10):2019–22.PubMedCrossRef Shakeri M, Boustani MR, Pak N, Panahi F, Salehpour F, Lotfinia I, et al. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Clin Neurol Neurosurg. 2013;115(10):2019–22.PubMedCrossRef
59.
go back to reference Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(2):R61.PubMedPubMedCentralCrossRef Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care. 2008;12(2):R61.PubMedPubMedCentralCrossRef
60.
go back to reference Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007;49(4):391–402 (e1–2).PubMedCrossRef Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007;49(4):391–402 (e1–2).PubMedCrossRef
61.
go back to reference Shakeri M, Boustani MR, Mahdkhah A. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Neurosurg Q. 2013;24(4):282–5.CrossRef Shakeri M, Boustani MR, Mahdkhah A. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Neurosurg Q. 2013;24(4):282–5.CrossRef
62.
go back to reference Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014;371(26):2467–76.PubMedCrossRef Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014;371(26):2467–76.PubMedCrossRef
63.
go back to reference Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014;371(26):2457–66.PubMedPubMedCentralCrossRef Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014;371(26):2457–66.PubMedPubMedCentralCrossRef
64.
65.
go back to reference Raj R, Skrifvars MB, Kivisaari R, Hernesniemi J, Lappalainen J, Siironen J. Acute alcohol intoxication and long-term outcome in patients with traumatic brain injury. J Neurotrauma. 2015;32(2):95–100.PubMedPubMedCentralCrossRef Raj R, Skrifvars MB, Kivisaari R, Hernesniemi J, Lappalainen J, Siironen J. Acute alcohol intoxication and long-term outcome in patients with traumatic brain injury. J Neurotrauma. 2015;32(2):95–100.PubMedPubMedCentralCrossRef
66.
go back to reference Pandit V, Patel N, Rhee P, Kulvatunyou N, Aziz H, Green DJ, et al. Effect of alcohol in traumatic brain injury: is it really protective? J Surg Res. 2014;190(2):634–9.PubMedCrossRef Pandit V, Patel N, Rhee P, Kulvatunyou N, Aziz H, Green DJ, et al. Effect of alcohol in traumatic brain injury: is it really protective? J Surg Res. 2014;190(2):634–9.PubMedCrossRef
67.
go back to reference Scheyerer MJ, Dutschler J, Billeter A, Zimmermann SM, Sprengel K, Werner CM, et al. Effect of elevated serum alcohol level on the outcome of severely injured patients. Emerg Med J. 2014;31(10):813–7.PubMedCrossRef Scheyerer MJ, Dutschler J, Billeter A, Zimmermann SM, Sprengel K, Werner CM, et al. Effect of elevated serum alcohol level on the outcome of severely injured patients. Emerg Med J. 2014;31(10):813–7.PubMedCrossRef
68.
go back to reference Cormio M, Gopinath SP, Valadka A, Robertson CS. Cerebral hemodynamic effects of pentobarbital coma in head-injured patients. J Neurotrauma. 1999;16(10):927–36.PubMedCrossRef Cormio M, Gopinath SP, Valadka A, Robertson CS. Cerebral hemodynamic effects of pentobarbital coma in head-injured patients. J Neurotrauma. 1999;16(10):927–36.PubMedCrossRef
69.
go back to reference Levin AB, Duff TA, Javid MJ. Treatment of increased intracranial pressure: a comparison of different hyperosmotic agents and the use of thiopental. Neurosurgery. 1979;5(5):570–5.PubMedCrossRef Levin AB, Duff TA, Javid MJ. Treatment of increased intracranial pressure: a comparison of different hyperosmotic agents and the use of thiopental. Neurosurgery. 1979;5(5):570–5.PubMedCrossRef
70.
go back to reference Schwartz ML, Tator CH, Rowed DW, Reid SR, Meguro K, Andrews DF. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Can J Neurol Sci. 1984;11(4):434–40.PubMedCrossRef Schwartz ML, Tator CH, Rowed DW, Reid SR, Meguro K, Andrews DF. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Can J Neurol Sci. 1984;11(4):434–40.PubMedCrossRef
71.
go back to reference Ward JD, Becker DP, Miller JD, Choi SC, Marmarou A, Wood C, et al. Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg. 1985;62(3):383–8.PubMedCrossRef Ward JD, Becker DP, Miller JD, Choi SC, Marmarou A, Wood C, et al. Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg. 1985;62(3):383–8.PubMedCrossRef
72.
go back to reference Majdan M, Mauritz W, Wilbacher I, Brazinova A, Rusnak M, Leitgeb J. Barbiturates use and its effects in patients with severe traumatic brain injury in five European countries. J Neurotrauma. 2013;30(1):23–9.PubMedPubMedCentralCrossRef Majdan M, Mauritz W, Wilbacher I, Brazinova A, Rusnak M, Leitgeb J. Barbiturates use and its effects in patients with severe traumatic brain injury in five European countries. J Neurotrauma. 2013;30(1):23–9.PubMedPubMedCentralCrossRef
73.
go back to reference Mellion SA, Bennett KS, Ellsworth GL, Moore K, Riva-Cambrin J, Metzger RR, et al. High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury. Pediatr Crit Care Med. 2013;14(3):239–47.PubMedCrossRef Mellion SA, Bennett KS, Ellsworth GL, Moore K, Riva-Cambrin J, Metzger RR, et al. High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury. Pediatr Crit Care Med. 2013;14(3):239–47.PubMedCrossRef
74.
go back to reference Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA. 2001;98(7):4044–9.PubMedPubMedCentralCrossRef Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA. 2001;98(7):4044–9.PubMedPubMedCentralCrossRef
75.
go back to reference Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC, et al. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA. 2014;312(1):36–47.PubMedPubMedCentralCrossRef Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC, et al. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA. 2014;312(1):36–47.PubMedPubMedCentralCrossRef
76.
go back to reference Aloizos S, Evodia E, Gourgiotis S, Isaia EC, Seretis C, Baltopoulos GJ. Neuroprotective effects of erythropoietin in patients with severe closed brain injury. Turk Neurosurg. 2015;25(4):552–8.PubMed Aloizos S, Evodia E, Gourgiotis S, Isaia EC, Seretis C, Baltopoulos GJ. Neuroprotective effects of erythropoietin in patients with severe closed brain injury. Turk Neurosurg. 2015;25(4):552–8.PubMed
77.
go back to reference Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, et al. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015;386(10012):2499–506.PubMedCrossRef Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, et al. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015;386(10012):2499–506.PubMedCrossRef
78.
go back to reference Concato J, Peduzzi P, Huang GD, O’Leary TJ, Kupersmith J. Comparative effectiveness research: what kind of studies do we need? J Invest Med. 2010;58(6):764–9.CrossRef Concato J, Peduzzi P, Huang GD, O’Leary TJ, Kupersmith J. Comparative effectiveness research: what kind of studies do we need? J Invest Med. 2010;58(6):764–9.CrossRef
Metadata
Title
Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature
Authors
Shaun E. Gruenbaum
Alexander Zlotnik
Benjamin F. Gruenbaum
Denise Hersey
Federico Bilotta
Publication date
01-09-2016
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 9/2016
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-016-0355-2

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