Protection of the ischemic brain by a new prostaglandin I2 analog clinprost

点击翻译按钮获取中文摘要

The 7-day infusion of a prostaglandin I2 analog TEI-7165 into the lateral ventricle of gerbils starting 2 hours before or just after 3-min forebrain ischemia is known to prevent the occurrence of learning disability and neuronal death in the hippocampal CA1 field. However, it remains to be determined whether or not intracerebroventricular infusion of TEI-7165 starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which TEI-7165 exerts a protective effect on ischemic hippocampal CA1 neurons also remains to be determined. In the first set of the present experiments, gerbils were infused with TEI-7165 for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. TEI-7165 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. In the second set of the present experiments, TEI-7165 prevented in vitro neuronal apoptosis or apoptotic neuron death caused by the nitric oxide (NO) donor sodium nitroprusside (SNP) in a concentration-dependent manner. Moreover, TEI-7165 (10^<-3>〜10^<-1> fg/ml) inhibited the expression of Bax, a proapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates a potent neuroprotective effect of TEI-7165 on ischemic hippocampal neurons in vivo possibly through inhibition of the expression of the proapoptotic factor, Bax.