The neuroprotective effects and mechanisms of L-type calcium channel agonist on ischemic neuronal death
会议名称：《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期：2009年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：L-type Ca2+ -channel ischemia hippocampus cell death ERK
摘 要：Objective Calcium overload is a dominant hypothesis for ischemic neuronal ***,we have reported previously that L-type Ca channel activity is downregulated in CA1 but not CA3 neurons at the late stage of reperfusion. The present study is to explore whether L-type Ca -channel agonist is protective on ischemic neuronal death and the underlying *** Hoechst and Niss1 staining were used to count neuronal death in cultured hippocampal neurons subjected to oxygen glucose deprivation(OGD) or in CA1 region of rats subjected to transient forebrain ischemia by four-vessel occlusion ***8644 was administered to rat by an osmotic pump pre-buried in the lateral ventricle. Morris water maze was used to detect the ability of spatial learning and *** blot analysis was used to assess the kinase activities of p38,JNK and ***(1) OGD induced about 40%neuronal death as detected at 24 h after ***8644 reduced nearly half of the cell death when administered at 1,3,6 or 12 h after OGD.L-type Ca -channel blockers,nifedipine or nimodipine,abolished the protective effects of BayK8644.(2) When tested in transient ischemia model in vivo,BayK8644(0.2 mM) administered at 12 h after reperfusion significantly enhanced the survival of CA1 neurons and improved the learning and memory,but lower concentration of BayK8644(0.1 mM) failed to protect neurons from death.(3) Phosphorylation of P38 and JNK transiently increased 30 min and restored at 1 h after *** of ERK decreased persistently and could be reversed by BayK8644 applied 12 h after *** addition,MEK inhibitor completely blocked the neuroprotective effect of *** L-type Ca -channel agonist protects hippocampal neurons from ischemia-induced cell death through activation of ERK.