Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury.
Riluzole (2-amino 6-trifluoromethoxy-benzothiazole) was studied in a rat model of traumatic brain injury (TBI) induced by a fluid percussion applied laterally to the right parietal cortex. Study I: vehicle or riluzole (4 or 8 mg/kg) was administered 15 min (i.v.), 6 h and 24 h (s.c.), after TBI. Brain lesions were quantified 1 week after insult. Riluzole significantly reduced the size of TBI-induced lesions by approximately 44% with either dose regime (P < 0.05). Study II: vehicle or riluzole (8 mg/kg) was administered 15 min (i.v.), 6 h (i.p.) and then twice daily (i.p.) for 6 days, after injury. One, 2 and 3 weeks after TBI, a neurological examination was performed. Control injured rats had a significant neurological deficit at 1, 2 and 3 weeks (P < 0.001). Riluzole treatment did not modify the neurological status evaluated for the first 2 weeks after TBI. However at 3 weeks, riluzole significant improved the neurological function of injured rats (P < 0.05). These results suggest that riluzole may be beneficial in the clinical treatment of TBI. The protective action of riluzole may result from (i) stabilization of the inactivated state of voltage-dependent sodium channels, (ii) indirect action on the glutamatergic pathway, and/or (iii) indirect neurotrophic effect.
Wahl
F
F
Rhône-Poulenc Rorer, Pharmaceuticals Discovery, Neurodegenerative Diseases Department, Vitry sur Seine, France. florence.wahl@rhone.poulenc.com
Renou
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E
Mary
V
V
Stutzmann
J M
JM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*; D014949:Wounds, Nonpenetrating / Q000473:pathology / Q000503:physiopathology
D018696:Neuroprotective Agents; D013844:Thiazoles; D019782:Riluzole