Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors.
To investigate the neuroprotective effect of taurine and the involved mechanisms, middle cerebral artery occlusion (MCAO) was induced with suture for 2h in rat, and the brain tissue was then reperfused. The infarct volume and cerebral damage area were measured, respectively, with 2,3,5-triphenyltetrazolium chloride (TTC) staining and MRI. Nissl staining was used for histological observation, and immunohistochemistry and Western-blot analysis for detecting the activated caspase-3 expression. Both pre- (200mgkg(-1)) and post-treatment of taurine decreased the neurology deficit score, infarct volume and brain water content. Taurine post-treatment (67, 200 and 600mgkg(-1)) showed a dose-dependent neuroprotective effect. Taurine (200mgkg(-1)) significantly decreased neuronal loss in the cerebral cortex and hippocampus, and reduced the expression of caspase-3 as well. The neuroprotective effect of taurine was partly blunted by strychnine or bicuculline alone, and almost completely blocked by coapplication of both antagonists of glycine and GABA(A) receptors. It is suggested that taurine exerts a neuroprotective role on the brain when administered before or after MCAO. Such effect is possibly mediated by the activation of both GABA(A) receptors and strychnine-sensitive glycine receptors. Moreover, inhibition of caspase-3 expression is involved in this neuroprotective effect. These results imply a potential therapeutic use of taurine for stroke.
Wang
Guo-Hua
GH
Institute of Nautical Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
Jiang
Zheng-Lin
ZL
Fan
Xing-Juan
XJ
Zhang
Lei
L
Li
Xia
X
Ke
Kai-Fu
KF
D000818:Animals; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013654:Taurine / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013818:Thermogravimetry
D018756:GABA Antagonists; D018696:Neuroprotective Agents; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013778:Tetrazolium Salts; D013654:Taurine; C009591:triphenyltetrazolium; D053148:Caspase 3