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

为研究选择性低温对大鼠局部脑血流量、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调节器。在第一年，局部脑温度和rCBF同时测量使用聚四氟乙烯涂层的铂电极和热电偶探头插入顶叶皮层和丘脑在自发性高血压大鼠（SHR）。第二年，结扎双侧颈总动脉造成前脑缺血1h，用酶法测定脑组织代谢物的浓度。当皮层温度低于30 ℃时，皮层和丘脑之间的局部脑温度差异更大。在缺血开始后立即诱导选择性脑低温（30 ℃）的大鼠中，三磷酸腺苷（ATP）水平显著高于正常对照组。 关于我们 常温大鼠（36 ℃）。我们的研究表明：1）新开发的脑温度调节器在小动物实验中是有用的，2）局部脑温度调节局部脑血流量，3）选择性脑低温治疗脑缺血是有效的和细胞保护的。我们研究了脑低温是否调节老年人海马脑缺血时兴奋性或抑制性氨基酸的释放。SHR使用微透析技术。在这项研究中，海马温度保持在36 ℃（正常体温）、33 ℃（轻度低温）或30 ℃（中度低温），直肠温度保持在37 ℃。脑缺血时，常温大鼠脑内谷氨酸、天冬氨酸和甘氨酸浓度分别显著升高至静息值的6倍、5倍和2倍，而低温则显著抑制其升高至静息值的220、110和80%。同样，在正常体温大鼠中牛磺酸的升高为16倍，在中度和轻度低温大鼠中显著减弱至3至10倍。亚低温还减弱了缺血引起的GABA升高。海马CA 1区缺血性损伤的组织学分级在7天后在中度亚低温大鼠（0.5 - <plus-minus>0.4）与常温组（1.8 - <plus-minus>0.3）相比显着改善。这些结果表明，脑低温保护老年SHR海马神经元免受缺血性损伤，这可能至少部分归因于保持突触稳态，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