Skip to main content
SpringerLink
Log in

Neuroprotective Effects of Riluzole in Neurotrauma Models: A Review

  • Conference paper
Current Progress in the Understanding of Secondary Brain Damage from Trauma and Ischemia

Part of the book series: Acta Neurochirurgica Supplements ((NEUROCHIRURGICA,volume 73))

Summary

Physical injury to the central nervous system (CNS) remains one of the main causes of mortality and disability in young adults. Numerous therapies have been successfully evaluated in experimental traumatic brain or spinal cord injuries (TBI, SCI) and, although some of them are currently under clinical trials for these indications, no drug therapy is at present available. Thus, an interesting approach to reduce the CNS injury-induced damage could be the blockade of Na+-channels by drugs such as riluzole which is neuroprotective in models of TBI or SCI as summarized in this review. Repeated doses ranging from 2 to 8mg/kg were administered between 24h to 10 days post-injury, with a first administration given either at 15 min or up to 6h post-injury. In these models riluzole was found to reduce both the size of spinal cord and brain lesions as well as brain edema, and to restore the neurological, motor and cognitive impairments consequent of these injuries. The largest therapeutic time window obtained was 1 to 6h in TBI. Thus such a compound should be considered as an interesting candidate for the treatment or SCI or TBI.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bareyre F, Wahl F, Mclntosh TK, Stutzmann J-M (1997) Time course of cerebral edema after traumatic brain injury in rats: effects of riluzole and mannitol. J Neurotrauma 11: 839–849

    Article  Google Scholar 

  2. Benavides J, Camelin C, Mitrani N, Flamand F, Uzan A, Legrand JJ, Gueremy C, Le Fur G (1985) 2-Amino-6-trifluoromethoxybenzothiazole, possible antagonist of excitatory amino acid neurotransmission. 2. Biochemical properties. Neuropharmacol 24: 1085–1092

    Article  CAS  Google Scholar 

  3. Benoît E, Escande D (1991) Riluzole specifically blocks inactivated Na+ channels in myelinated nerve fibre. Pflügers Arch 419: 603–609

    Article  PubMed  Google Scholar 

  4. Chéramy A, Barbeito L, Godeheu G, Glowinski J (1992) Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo. Neurosci Lett 147: 209–212

    Article  PubMed  Google Scholar 

  5. Dargent B, Arsac C, Tricaud N, Couraud F (1996) Activation of voltage-dependent sodium channels in cultured cerebellar granule cells induces neurotoxicity that is not mediated by glutamate release. Neurosci 73: 209–216

    Article  CAS  Google Scholar 

  6. Debono MW, Le Guern J, Canton T, Doble A, Pradier L (1993) Inhibition by riluzole of electrophysiological responses mediated by kainate and NMDA receptors expressed in Xenopus oocytes. Eur J Pharmacol 235: 283–289

    Article  PubMed  CAS  Google Scholar 

  7. De Ryck M (1997) Protection of neurological function in stroke models and neuroprotective properties of lubeluzole. Cere-brovasc Dis 7 [Suppl] 1: 18–30

    Google Scholar 

  8. Dietrich WD (1992) The importance of brain temperature in cerebral injury. J Neurotrauma 9: S475–S485

    PubMed  Google Scholar 

  9. Doble A (1996) The pharmacology and mechanism of action of riluzole. Neurology 47 [Suppl] 4: S233–S241

    Google Scholar 

  10. Doppenberg EMR, Bullock R (1997) Clinical neuro-protection trials in severe traumatic brain injury: lessons from previous studies. J Neurotrauma 14: 71–80

    Article  PubMed  CAS  Google Scholar 

  11. Dunn LT (1997) Clinical trial reports-central & peripheral nervous system-head injury therapies. Exp Opin Invest Drugs 6: 1511–1526

    Article  CAS  Google Scholar 

  12. Farooque M, Hillered L, Holtz A, Olsson Y (1996) Changes in extracellular levels of amino acids after graded compression trauma to the spinal cord: an experimental study in the rat using microdialysis. J Neurotrauma 13: 537–548

    Article  PubMed  CAS  Google Scholar 

  13. Fineman I, Hovda DA, Smith M, Yoshino A, Becker DP (1993) Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Res 624: 94–102

    Article  PubMed  CAS  Google Scholar 

  14. Girdlestone D, Dupuy A, Coston A et al Roy-Contauciu L Jscaude D (1989) Riluzole antagonizes excitatory amino acid-evoked firing in rat facial motoneurons in vivo. Br J Pharmacol [Suppl] 97: 583P

    Google Scholar 

  15. Globus MYT, Alonso O, Dietrich WD, Busto R, Ginsberg MD (1995) Glutamate release and free radicals production following TBI: effects of post-traumatic hypothermia. J Neurochem 65: 1704–1711

    Article  PubMed  CAS  Google Scholar 

  16. Grotta J, for the US and Canadian lubeluzole ischemic stroke study group (1997) Lubeluzole treatment of acute ischemic stroke. Stroke 28: 2338–2346

    Article  PubMed  CAS  Google Scholar 

  17. Gurney ME, Fleck TJ, Hirnes CS, Hall ED (1998) Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology 50: 62–66

    Article  PubMed  CAS  Google Scholar 

  18. Hamm FJ, O’Dell DM, Pike BR, Lyeth BG (1993) Cognitive impairment following traumatic brain injury: the effect of pre-and post-injury administration of scopolamine and MK-801. Cogn Brain Res 1: 223–226

    Article  CAS  Google Scholar 

  19. Hubert JP, Delumeau JC, Glowinski J, Premont J, Doble A (1992) Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured grnaule cells: evidence for a dual mechanism of action. Br J Pharmacol 113: 261–267

    Article  Google Scholar 

  20. Janis LS, Stein DG (1996) Intraseptal injections of NGF attenuates edema formation following septal lesions in the rat. Neurosci Lett 214: 21–24

    Article  PubMed  CAS  Google Scholar 

  21. Katayama Y, Becker DP, Tamura T, Hovda DA (1990) Massive increases in extracellular potassium and the indiscriminativerelease of glutamate following concussive brain injury. J Neu-rosurg 73: 889–900

    CAS  Google Scholar 

  22. Kwon J-Y, Bacher A, Zornow MH (1998) Riluzole does not attenuate increases in hippocampal glutamate concentrations in a rabbit model of repeated transient global cerebral ischemia. AnesthAnalg 86: 128–133

    Article  CAS  Google Scholar 

  23. Leach MJ, Swan JH, Eisenthal D, Dopson M, Nobbs M (1993) BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke 24: 1063–1067

    Article  PubMed  CAS  Google Scholar 

  24. McDermott KL, Raghupathi R, Fernandez SC, Saatman KE, Protter AA, Finklestein SP, Sinson G, Smith DH, Mclntosh TK (1997) Delayed administration of basic fibroblast growth factor (bFGF) attenuates cognitive dysfunction following parasagittal fluid percussion brain injury in the rat. J Neurotrauma 14: 191–200

    Article  PubMed  CAS  Google Scholar 

  25. Mclntosh TK (1993) Novel pharmacologie therapies in the treatment of experimental traumatic brain injury: a review. J Neurotrauma 10: 215–261

    Article  Google Scholar 

  26. Mclntosh TK, Smith DH, Voddi M, Perri BR, Stutzmann J-M (1996) Riluzole, a novel neuroprotective agent attenuates both neurological motor and cognitive dysfunction following experimental brain injury in the rat. J Neurotrauma 13: 767–780

    Article  Google Scholar 

  27. Nilsson P, Laursen H, Hillered L, Hansen AJ (1996) Calcium movements in traumatic brain injury: the role of glutamate receptor-gated ion channels. J Cereb Blood Flow Metab 16: 262–270

    Article  PubMed  CAS  Google Scholar 

  28. Obrenovitch TP, Urenjak J (1997) Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury. J Neurotrauma 10: 677–698

    Article  Google Scholar 

  29. Palmer AM, Marion DW, Botscheller ML, Bowen DM, Dekosky ST (1994) Increased transmitter amino acid concentration in human ventricular CSF after brain trauma. Neuroreport 6: 153–156

    Article  PubMed  CAS  Google Scholar 

  30. Peluffo H, Estevez A, Barbeito L, Stutzmann J-M (1997) Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers. Neurosci Lett 228: 207–211

    Article  PubMed  CAS  Google Scholar 

  31. Sanderson KL, Saatman KE, Fernandez SC, McDermott KL, Contreras P, Mclntosh TK (1996) Continuous infusion of insulin-like growth factor-1 (IGF-1) attenuates neurological motor and cognitive deficits following experimental brain injury in the rat. J Neurotrauma 13: 626

    Google Scholar 

  32. Stutzmann J-M, Pratt J, Boraud T, Gross C (1996) The effect of riluzole on post-traumatic spinal cord injury in the rat. Neuroreport 7: 387–392

    Article  PubMed  CAS  Google Scholar 

  33. Stutzmann J-M, Wahl F, Pratt J, Mary V, Reibaud M, Tecoult E, Rataud J (1997) Neuroprotective profile of riluzole in in vivo models of acute neurodegenerative diseases. CNS Drug Rev 3: 83–101

    Article  CAS  Google Scholar 

  34. Sun FY, Faden AI (1995) Neuroprotective effects of 619C89, a use-dependent sodium channel blocker, in rat traumatic brain injury. Brain Res 673: 133–140

    Article  PubMed  CAS  Google Scholar 

  35. Toulmond S, Duval D, Serrano A, Benavides J (1993) Biochemical and histological alterations induced by fluid percussion brain injury in the rat. Brain Res 620: 24–31

    Article  PubMed  CAS  Google Scholar 

  36. Toulmond S, Duval D, Serrano A, Scatton B, Benavides J (1993) Prevention by eliprodil (SL82.0715) of traumatic brain damage in the rat. Existence of a large (18h) therapeutic window. Brain Res 620: 32–41

    CAS  Google Scholar 

  37. Urenjak J, Obrenovitch TP (1997) Pharmacological modulation of sodium channels by riluzole: an alternative to antiexcitotoxic actions. Rev Contemp Pharmacothera 8: 237–246

    CAS  Google Scholar 

  38. Varon S, Conner JM (1994) Nerve growth factors in CNS repair. J Neurotrauma 11: 473–486

    Article  PubMed  CAS  Google Scholar 

  39. Voddi MD, Perri BR, Perlman KG, Smith DH, Leach M, McIntosh TK (1995) The use-dependent sodium channel antagonist 619C89 attenuates memory dysfunction following experimental brain injury. J Neurotrauma 12: 146

    Google Scholar 

  40. Wahl F, Renou E, Mary V, Stutzmann J-M (1997) Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury. Brain Res 756: 247–255

    Article  PubMed  CAS  Google Scholar 

  41. Wokke J (1996) Riluzole. Lancet 348: 795–799

    Article  PubMed  CAS  Google Scholar 

  42. Zhang C, Raghupathi C, Saatman KE, Smith DH, Stutzmann JM, Wahl F, Mclntosh TK (1997) Effects of riluzole on cortical damage following brain trauma. J Neurotrauma 14: 799

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurodegenerative Diseases Department, Rhône-Poulenc Rorer, 94403, CRVA Cedex, France

    Dr. F. Wahl & J.-M. Stutzmann

Authors
  1. Dr. F. Wahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.-M. Stutzmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Chirurgische Forschung, Ludwig-Maximilians-Universität, Klinikum Grosshadern, München, Germany

    Alexander Baethmann , Nikolaus Plesnila , Florian Ringel  & Jörg Eriskat , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Wien

About this paper

Cite this paper

Wahl, F., Stutzmann, JM. (1999). Neuroprotective Effects of Riluzole in Neurotrauma Models: A Review. In: Baethmann, A., Plesnila, N., Ringel, F., Eriskat, J. (eds) Current Progress in the Understanding of Secondary Brain Damage from Trauma and Ischemia. Acta Neurochirurgica Supplements, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6391-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6391-7_18

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-7312-1

  • Online ISBN: 978-3-7091-6391-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation