Development of factors that prevent secondary neuronal degeneration

点击翻译按钮获取中文摘要

The 7-day infusion of a prosaposin-related 18-mer peptide (18-MP) 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 the 18-MP starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which the 18-MP 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 the 18-MP for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. 18-MP 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 the 18-MP than in those receiving vehicle infusion. In the second set of the present experiments, the 18-MP 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, the 18-MP (1-10^5 fg/ml) increased the expression of Bcl-x_L, an antiapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates that the 18-MP prevents secondary neuronal degeneration after ischemia in vivo possibly through an increase in the expression of the antiapoptotic factor, Bcl-x_L.