Effect of riluzole on focal cerebral ischemia in rats.
The effects of riluzole, a putative inhibitor of glutamate release, on the histological and neurobehavioral consequences of middle cerebral artery occlusion were tested in Sprague-Dawley rats. Neurobehavioral studies (neurological examination, passive avoidance task) were carried out with sham-operated and occluded rats. Riluzole 4 and 8 mg/kg administered 30 min after occlusion reduced (P < 0.01) the cortical infarct (respectively 94 +/- 12 mm3 and 73 +/- 15 mm3 versus 139 +/- 8 mm3 for control rats). Striatum necrosis was not modified by the low dosage (46 +/- 3 mm3 versus 49 +/- 3 mm3 for control rats), whereas the high dosage increased it (61 +/- 3 mm3, P < 0.05). The ischemia-induced neurological and memory impairments were not improved by riluzole. Our results indicate that a drug depressing glutamatergic neurotransmission without blocking the glutamate receptors exerts anti-ischemic activity. Moreover, the results highlight the need for carrying out histological and neurobehavioral studies in parallel in this model.
Wahl
F
F
Université René Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacologie, Paris, France.
Allix
M
M
Plotkine
M
M
Boulu
R G
RG
D000777:Anesthetics / Q000627:therapeutic use*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects; D019782:Riluzole; D013844:Thiazoles / Q000627:therapeutic use*
D000777:Anesthetics; D017470:Receptors, Glutamate; D013844:Thiazoles; D019782:Riluzole