EFFECT OF MILD HYPOTHERMIA ON ISCHEMIA-INDUCED RELEASE OF NEUROTRANSMITTERS AND FREE FATTY-ACIDS IN RAT-BRAIN
EFFECT OF MILD HYPOTHERMIA ON ISCHEMIA-INDUCED RELEASE OF NEUROTRANSMITTERS AND FREE FATTY-ACIDS IN RAT-BRAIN
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DOI：
10.1161/01.str.20.7.904
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发表时间：
1989-07-01
期刊：
影响因子：
8.3
通讯作者：
GINSBERG, MD
中科院分区：
文献类型：
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作者：
BUSTO, R;GLOBUS, MY;GINSBERG, MD
我们先前已经证明，轻度缺血内低温对最终的组织病理学结果具有显著的保护作用。本研究旨在评估这种保护作用是否涉及局部脑血流量减少程度的变化、游离脂肪酸的组织蓄积或谷氨酸和多巴胺细胞外释放的改变。缺血期脑温度维持在36 ℃的大鼠。C，33度。C，或30 ℃。C组采用四血管阻断联合全身降压的方法进行缺血20分钟。局部脑血流量水平，放射自显影测量，在缺血期结束时，在所有实验动物均匀减少。皮质和纹状体游离脂肪酸水平测定缺血结束时，组织提取和分离后，通过气相色谱薄层色谱法。在局部缺血时脑温度保持在36 ℃或38 ℃的动物组中观察到大量局部缺血诱导的单个游离脂肪酸的积累。C或30 ℃。C.细胞外神经递质水平测定微透析;灌流液收集前，期间和缺血后。在局部缺血脑温度维持在36 ℃的大鼠中，C、多巴胺和谷氨酸在缺血和再循环早期显著增加（分别增加500倍和7倍）。在脑温维持在33 ℃的动物中，C和30度。C时，谷氨酸的释放被完全抑制，多巴胺的释放明显减弱（减少60%）。结果提示，轻度缺血内低温不影响缺血引起的局部脑血流量减少或游离脂肪酸蓄积。脑温度的微小变化发挥其保护作用的机制之一可能涉及减少缺血诱导的谷氨酸和多巴胺释放。
We have demonstrated previously that mild intraischemic hypothermia confers a marked protective effect on the final histopathological outcome. The present study was carried out to evaluate whether this protective effect involves changes in the degree of local cerebral blood flow reductions, tissue accumulation of free fatty acids, or alterations in the extracellular release of glutamate and dopamine. Rats whose intraischemic brain temperature was maintained at 36.degree. C, 33.degree. C, or 30.degree. C were subjected to 20 minutes of ischemia by four-vessel occlusion combined with systemic hypotension. Levels of local cerebral blood flow, as measured autoradiographically, were reduced uniformly in all experimental animals at the end of the ischemic period. Cortical and striatal free fatty acid levels were measured at the end of ischemia by gas chromatography after tissue extraction and separation by thin layer chromatography. A massive ischemia-induced accumulation of individual free fatty acids was observed in animal groups whose intraischemic brain temperature was maintained at either 36.degree. C or 30.degree. C. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. In rats whose intraischemic brain temperature was maintained at 36.degree. C, dopamine and glutamate increased significantly during ischemia and the early period of recirculation (by 500-fold and sevenfold, respectively). In animals whose brain temperature was maintained at 33.degree. C and 30.degree. C, the release of glutamate was completely inhibited, and the release of dopamine was significantly attenuated (by 60%). These results suggest that mild intraischemic hypothermia does not affect the ischemia-induced local cerebral blood flow reduction or free fatty acid accumulation. One of the mechanisms by which small variations in brain temperature exert their protective effect may involve the reduction of ischemia-induced glutamate and dopamine release.