P/Q-type Ca2+ channel blocker omega-agatoxin IVA protects against brain injury after focal ischemia in rats.
Recently, P/Q-type Ca2+ channels have been shown to be involved in neurotransmission in the central nervous system in mammals. We evaluated the effects of the P/Q-type Ca2+ channel blocker omega-agatoxin IVA (omega-Aga-IVA) on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery (MCA) occlusion in rats. Intracerebroventricular (i.c.v.) treatment with omega-Aga-IVA significantly attenuated the postischemic increase of brain water content. omega-Aga-IVA also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. omega-Aga-IVA (30 pmol, i.c.v.), which exhibited a neuroprotective effect, had no significant effect on the magnitude of intra- and postischemic brain temperature when compared with vehicle-treated rats. This indicates that the postischemic neuroprotective effect of omega-Aga-IVA is produced by a direct and not an indirect effect via hypothermia. These results suggest that P/Q-type Ca2+ channels may be involved in the development of focal ischemic brain injury and that blockers of these channels may be therapeutically useful against ischemic injury.
Asakura
K
K
Discovery Research Laboratories II, Shionogi and Co. Ltd., Osaka, Japan.
Matsuo
Y
Y
Kanemasa
T
T
Ninomiya
M
M
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology; D003243:Consciousness; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy; D013111:Spider Venoms / Q000494:pharmacology*; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D013111:Spider Venoms; D020867:omega-Agatoxin IVA