Skip to main content
SpringerLink
Log in

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

  • Systematic Review
  • Published:
CNS Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  3. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  17. Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Horm Behav. 2013;63(2):331–44.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  29. Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981;8(1):10–4.

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42(4):515–24.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kelly DF. Alcohol and head injury: an issue revisited. J Neurotrauma. 1995;12(5):883–90.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA

      Shaun E. Gruenbaum & Benjamin F. Gruenbaum

    2. Department of Anesthesiology and Critical Care, Ben-Gurion University of the Negev, 84101, Beer-Sheva, Israel

      Alexander Zlotnik

    3. Cushing/Whitney Medical Library, Yale University, New Haven, CT, USA

      Denise Hersey

    4. Department of Anesthesiology, Critical Care and Pain Medicine, ‘La Sapienza’ University of Rome, Piazzale Aldo Moro, 5, 00185, Rome, Italy

      Federico Bilotta

    Authors
    1. Shaun E. Gruenbaum
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Alexander Zlotnik
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Benjamin F. Gruenbaum
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Denise Hersey
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Federico Bilotta
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Federico Bilotta.

    Ethics declarations

    Funding

    Shaun Gruenbaum is an Investigative Medicine MD to PhD Program graduate student. This publication was made possible by Clinical and Translational Science Awards (CTSA) Grant number UL1 TR000142 from the National Center for Advancing Translational Science (NCATS), a component of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH.

    Conflicts of interest

    Shaun Gruenbaum, Alexander Zlotnik, Benjamin Gruenbaum, Denise Hersey, and Federico Bilotta declare no conflicts of interest.

    Additional information

    S. E. Gruenbaum and A. Zlotnik contributed equally to this article.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (PDF 77 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Gruenbaum, S.E., Zlotnik, A., Gruenbaum, B.F. et al. Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature. CNS Drugs 30, 791–806 (2016). https://doi.org/10.1007/s40263-016-0355-2

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40263-016-0355-2

    Keywords

    Search

    Navigation