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

CNS Drugs

Volumn 30, Issue 9, 2016, Pages 791-806

  Gruenbaum, Shaun E ^a   Zlotnik, Alexander ^b   Gruenbaum, Benjamin F ^a   Hersey, Denise ^a   Bilotta, Federico ^c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ALCOHOL; ANTICONVULSIVE AGENT; BARBITURIC ACID DERIVATIVE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CANNABIS; CEREBROLYSIN; CYCLOSPORIN A; ENZOGENOL; ERYTHROPOIETIN; GLIBENCLAMIDE; GROWTH HORMONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; NITRIC OXIDE SYNTHASE INHIBITOR; PROGESTERONE; RONOPTERIN; UNCLASSIFIED DRUG; NEUROPROTECTIVE AGENT;

CASE STUDY; CLINICAL OUTCOME; COHORT ANALYSIS; DRUG THERAPY; HUMAN; IN VITRO STUDY; MEDICAL RECORD REVIEW; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMATIC REVIEW; TRAUMATIC BRAIN INJURY; HOSPITAL EMERGENCY SERVICE; INTENSIVE CARE UNIT; INTRACRANIAL PRESSURE; PATHOPHYSIOLOGY; TIME FACTOR; TREATMENT OUTCOME;

BRAIN INJURIES, TRAUMATIC; EMERGENCY SERVICE, HOSPITAL; HUMANS; INTENSIVE CARE UNITS; INTRACRANIAL PRESSURE; NEUROPROTECTIVE AGENTS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TIME FACTORS; TREATMENT OUTCOME;

EID: 84976319225     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.1007/s40263-016-0355-2     Document Type: Review

References (78)

1. 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.
2. 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.
3. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Stocchetti N, Paterno R, Citerio G, Beretta L, Colombo A. Traumatic brain injury in an aging population. J Neurotrauma. 2012;29(6):1119–25.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Horm Behav. 2013;63(2):331–44.
18. 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.
19. 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).
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981;8(1):10–4.
30. 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).
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.
46. 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.
47. 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.
48. Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.
54. 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).
55. 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.
56. 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.
57. 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.
58. 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.
59. 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.
60. 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).
61. 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.
62. 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.
63. 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.
64. Kelly DF. Alcohol and head injury: an issue revisited. J Neurotrauma. 1995;12(5):883–90.
65. 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.
66. 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. 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.
72. 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.
73. 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.
74. 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.
75. 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.
76. 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.
77. 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.
78. 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.