[Neuroprotection of chloride channel blockers against NMDA-induced apoptosis of cultured rat hippocampal neurons].
Activation of N-methyl-d-aspartic acid (NMDA) receptor plays an important role in neuronal apoptosis induced by cerebral ischemia but the underlying mechanisms are still unclear. The present study examined the neuroprotection of three chloride blockers in an in vitro cell model of cerebral ischemia established by treatment of cultured rat hippocampal neurons with NMDA. Hoechst 33258 staining and MTT assay were used to detect neuronal apoptosis and cell viability, respectively. The neuroprotective effects of chloride channel blockers on the cell viability and neuronal apoptosis were only observed when the blockers were applied before NMDA exposure. In comparison with DIDS, SITS showed more potent protective effect in a dose-dependent manner, whereas NPPB showed no significant neuroprotective effect. The results demonstrate that pretreatment with both SITS and DIDS have protective effect against neuronal apoptosis, which is achieved by blocking both NMDA receptor and chloride channel.
Chang
Quan-zhong
QZ
Department of Neurobiology, Southern Medical University, Guangzhou 510515, China. qzchang@tom.com
Hu
De-hui
DH
Chen
Ming
M
Wang
Ying
Y
Gao
Tian-ming
TM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000166:cytology; D008856:Microscopy, Fluorescence; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018118:Chloride Channels; D018696:Neuroprotective Agents; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D016202:N-Methylaspartate; D006690:Bisbenzimidazole; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid