Quantitative Analysis of Learning and Memory Function and Chemical Neurotransmission in Experimental Cerebral Ischemia.

用定量放射自显影方法研究了沙土鼠实验性脑缺血时第二信使系统腺苷环化酶(AC)和蛋白激酶C(PKC)及局部脑血流量(LCBF)的变化，使这三个参数可以在同一脑内测量。结扎右侧颈总动脉6h造成大鼠脑缺血。缺血评分达到5分以上的动物被用于进一步的实验。缺血结束后，采用[14&gt；C]碘安替比林法测定LCBF。AC和PKC活性分别用~(3 H)Forsklin(FK)和[~(3 H)]佛波醇12，13-二丁酸酯(PDBu)放射自显影技术测定。健侧大部分脑区LCBF降至10ml/100g/min以下。FK结合强度在嗅结节、尾壳核和苍白球的减少最大，其次是海马区和大脑皮质。在LCBF&lt；-20ml/100g/min时，大脑皮层FK结合量较低，而PDBU结合量在大脑各结构中保存较好，大脑皮层LCBF与PDBU结合量之间无显著相关性。在其他研究中，我们观察到AC和PKC系统在缺血后2小时在缺血侧受到刺激，这表明第二信使系统在缺血时相可能对缺血做出不同的反应。

Alterations of the second-messenger systems, adenylate cyclase (AC) and protein kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during experimental cerebral ischemia in gerbils employing a quantitative autoradiographic method, which permitted these three parameters to be measured in the same brain. Ischemia was induced by occlusion of the right common carotid artery for 6 hours. Animals attaining more than 5 in their ischemic scores were utilized for further experiments. At the end of ischemia, lCBF was measured by the [ ^<14>C]iodoantipyrine method. The AC and PKC activities were estimated by the agtoradiographic technique developed in our laboratory using[ ^3H]forskolin (FK) and [ ^3H]phorbol 12, 13dibutyrate (PDBu), respectively. The lCBF fell below 10 ml/100g/min in most cerebral regions on theligated side. The greatest reduction of FK binding was noted in the olfactory tubercle, caudate-putamen and globus pallidus, followed by the hippocampus and cerebral cortices. The FK binding tended to be low at lCBF<-20 ml/100g/min in the cerebral cortices, However, the PDBU binding was relatively well preserved in each cerebral structure, and no significant correlation between lCBF and PDBU binding was noted in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult over extensive brain regions, while the PKC system may be relatively resistant to ischemia.In additional studies, we observed that the AC and PKC systems were stimulated on the ischemic side at 2 hours after ischemia, suggesting that the second-messenger systems may respond to ischemia differently in terms of the phase of ischemia.