Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia.
Talampanel (IVAX) is a non-competitive AMPA-antagonist has a remarkable neuroprotection in different rodent stroke models. The focal cerebral ischemia in mice was induced by transient (60 min.) MCA occlusion and 48 h reperfusion and treated with talampanel (6 x 2 mg/kg, i.p.). The apoptotic and necrotic cells were analyzed by double immune histochemical staining on confocal laser microscope. The infarct size is decreased significantly by talampanel treatment (from 57.1+/-7.2mm(2) to 18.9+/-2.6 mm(2), p< 0.001). The number of TUNEL-positive cells localized mostly in the border zone of ischemic lesions is significantly decreased after talampanel treatment (from 962+/-13.0 to 604+/-6.9, p < 0.01). A strong, significant reduction of caspase-3 active cells was visualized. Talampanel as a neuroprotective drug candidate has a significant effect in mice transient MCA occlusion model.
Denes
L
L
Department of Vascular Neurology, National Institute of Neurology and Psychiatry, Budapest, Hungary. denes42@opni.hu
Szilágyi
G
G
Gál
A
A
Nagy
Z
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D001569:Benzodiazepines; C085266:talampanel; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases