Effect of Selective Brain Hypothermia on Regional Cerebral Blood Flow, Brain Tissue Metabolites and Neurotransmitter Release in Spontaneously Hypertensive Rats

为了研究选择性低温对大鼠局部脑血流量（rCBF）、脑组织代谢和神经递质释放的影响，我们研制了一种小动物脑温度调节剂。第一年，在自发性高血压大鼠（SHR）的顶叶皮层和丘脑中插入一种特氟龙涂层复合铂电极和热电偶探针，同时测量脑区域温度和rCBF。第二年，结扎双侧颈动脉诱导前脑缺血1小时，用酶法测定脑组织代谢物浓度。当皮层温度设定在30ººC比37ººC低时，大脑皮层和丘脑的区域温度差异更大。在缺血开始后立即诱导的选择性脑低温（30 C）大鼠中，三磷酸腺苷（ATP）水平显著高于正常大鼠（36 C）。我们的研究表明：1)新开发的脑热调节剂在小动物实验中是有用的；2)局部脑温度调节区域脑血流量；3)选择性脑低温对脑缺血的治疗是有效的和细胞保护的。在最后一年，我们使用微透析技术研究了脑低温是否会调节老年SHR海马脑缺血期间兴奋性或抑制性氨基酸的释放。在本研究中，海马温度维持在36ºC（常温）、33ºC（亚低温）或30ºC（中低温），直肠温度维持在37ºC。在脑缺血时，正常体温大鼠的谷氨酸、天冬氨酸和甘氨酸浓度分别比静息值显著增加6倍、5倍和2倍，而低温则显著抑制其升至静息值的220,110和80%。同样，在常温大鼠中牛磺酸升高16倍，在中度和轻度低温大鼠中显著降低到3- 10倍。低温也能减弱缺血引起的GABA升高。与常温大鼠（1.8 <正负> 0.3）相比，中低温大鼠7天后海马CA1区缺血损伤的组织病理学分级（0.5 <正负> 0.4）明显改善。这些结果表明，脑低温可以保护老年SHR海马神经元免受缺血性损伤，这可能至少部分归因于突触内平衡的保存，防止兴奋性和抑制性氨基酸的过度释放

To investigate the effect of selective hypothermia on regional cerebral blood flow (rCBF), brain tissue metabolism and neurotransmitter release in rats, we newly developed a brain thermoregulator for small animals. In the first year, regional brain temperature and rCBF were simultaneously measured using a Teflon-coated combined platinum electrode and thermocouple probe inserted into the parietal cortex and the thalamus in spontaneously hypertensive rats (SHR). In the second year, one hour of forebrain ischemia was induced by bilateral carotid artery ligation, and the concentrations of brain tissue metabolites were measured enzymatically. The difference in regional brain temperature between the cortex and the thalamus became greater when cortical temperature was set to the lower level such as 30ﾟC than 37ﾟC.In the rats induced selective brain hypothermia (30ﾟC) immediately after the initiation of ischemia, the level of adenosine triphosphate (ATP) was significantly higher than that in n … More ormothermic rats (36ﾟC). Our study suggests 1) the newly developed brain thermo-regulator is useful in the small animal experiments, 2) regional brain temperature regulates regional cerebral blood flow, and 3) selective brain hypothermia is effective and cytoprotective in the treatment of brain ischemia.In the final year, we examined whether brain hypothermia modulates the release of excitatory or inhibitory amino acids during cerebral ischemia in the hippocampus of aged SHR using a microdialysis technique. Hippocampal temperature was maintained 36ﾟC (normothermia), 33ﾟC (mild hypothermia) or 30ﾟC (moderate hypothermia), and rectal temperature 37ﾟC in this study. During cerebral ischemia, concentrations of glutamate, aspartate and glycine significantly increased 6-, 5-and 2-fold the resting values, respectively, in the normothermic rats, whereas hypothermia markedly inhibited the rise to 220,110 and 80% of the resting values. Similarly the elevation of taurine was 16-fold in the normothermic rats and significantly attenuated to 3-to 10-fold in both moderately and mildly hypothermic rats. The hypothermia also attenuated the ischemia-induced elevation of GABA.Histopathological grading of ischemic damage in the hippocampal CA1 areas after 7 days was significantly ameliorated in the moderate hypothermic rats (0.5 <plus-minus> 0.4) compared with the normothermic ones (1.8 <plus-minus> 0.3). These results suggest that brain hypothermia protects the neurons against ischemic insult in the hippocampus of aged SHR,and it may be, at least in part, attributed to the preservation of synaptic homeostasis preventing the excessive release of both excitatory and inhibitory amino ac Less