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

采用放射自显影定量方法，对沙土鼠实验性脑缺血过程中第二信使系统、腺苷酸环化酶（AC）和蛋白激酶C（PKC）以及局部脑血流量（lCBF）的变化进行了研究。通过闭塞右颈总动脉6小时诱导缺血。将缺血评分超过5的动物用于进一步的实验。在缺血结束时，通过[ ^<14>C]碘安替比林法测量lCBF。AC和PKC活性分别用[ ^3H]forskolin（FK）和[ ^3H]佛波醇12，13-二丁酸酯（PDBu）用放射性同位素示踪技术测定。结扎侧大部分脑区lCBF低于10 ml/100 g/min。FK结合的最大减少是在嗅结节，尾壳核和苍白球，其次是海马和大脑皮质。当lCBF&lt;-20 ml/100 g/min时，FK结合率降低，而PDBU结合率在各脑结构中保持较好，两者之间无明显相关性。AC系统因此可能是易受缺血损伤的广泛的脑区，而PKC系统可能是相对耐缺血。在另外的研究中，我们观察到，AC和PKC系统在缺血后2小时在缺血侧被刺激，这表明第二信使系统可能对缺血不同的缺血反应在缺血的阶段。

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.