Zhang Hong, Zhou Min, Zhang Junjian, Mei Yuanwu, Sun Shenggang, Tong Etang
Department of Neurology, Zhongnan Hospital of Wuhan University, and Center for Cerebral Vascular Diseases, Medical College of Wuhan University, Wuhan 430071, China.
Neurol Res. 2008 May;30(4):332-6. doi: 10.1179/174313208X300279.
To study the efficacy of post-ischemic mild brain hypothermia lasting for different time intervals on cerebral ischemic reperfusion injury.
Male Sprague-Dawley rats were divided into a sham-operated group, normothermia (37-38 degrees C) ischemia group and mild hypothermia (31-32 degrees C) group. The last group was subdivided into four groups: 30 minute hypothermia plus 210 minute normothermia, 60 minute hypothermia plus 180 minute nomothermia,120 minute hypothermia plus 120 minute normothermia, and 240 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model. Brain tissue was collected following a 20 minute cerebral ischemia and 240 minute reperfusion, and was used to measure the levels of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin(5-HT) and hydroxyindoleacetic acid (5-HIAA), nitrite (NO(2)), endothelin-1 (ET(1)), tumor necrosis factor alpha(TNFalpha) and interleukin-1beta (IL-1beta). Serum was collected to measure the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and its brain band isoenzyme (CK-BB).
Hypothermia lasting for 60-240 minutes delayed the decrease in these amino acids, postponed the decrease in DA, NE and 5-HT and increase in hydroxyindoleacetic acid (5-HIAA), and decreased the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue. Hypothermia also decreased the levels of LDH, AST, CK and CK-BB in serum as compared to normothermia group (p<0.05 or p<0.01). Hypothermia lasting for 30 minutes delayed the decreases in these amino acids and 5-HT and increase in 5-HIAA in brain tissue (p<0.05), but failed to influence the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue and the amounts of LDH, AST, CK and CK-BB in serum as compared to normothermia ischemia group (p>0.05).
Post-ischemic mild brain hypothermia can significantly suppress the excessive release of amino acids, monoamine neurotransmitters and inflammation response in ischemic tissue. It can also stabilize the function of the cell membrane, which is associated with the mechanism of cerebral protection by mild hypothermia. These results suggest that mild hypothermia should be applied immediately after ischemia and last for more than 60 minutes in order to obtain neuroprotective effects.
研究缺血后不同时长的轻度脑低温对脑缺血再灌注损伤的疗效。
将雄性Sprague-Dawley大鼠分为假手术组、正常体温（37 - 38摄氏度）缺血组和轻度低温（31 - 32摄氏度）组。最后一组再细分为四组：30分钟低温加210分钟正常体温组、60分钟低温加180分钟正常体温组、120分钟低温加120分钟正常体温组和240分钟低温组（n = 8）。采用Pulsinelli四血管闭塞模型建立全脑缺血。在脑缺血20分钟和再灌注240分钟后收集脑组织，用于测量谷氨酸（Glu）、天冬氨酸（Asp）、甘氨酸（Gly）、γ-氨基丁酸（GABA）、多巴胺（DA）、去甲肾上腺素（NE）、5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）、亚硝酸盐（NO₂）、内皮素-1（ET₁）、肿瘤坏死因子α（TNFα）和白细胞介素-1β（IL-1β）的水平。收集血清以测量乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）、肌酸激酶（CK）及其脑型同工酶（CK-BB）的水平。
持续60 - 240分钟的低温延缓了这些氨基酸水平的下降，推迟了DA、NE和5-HT水平的降低以及5-羟吲哚乙酸（5-HIAA）水平的升高，并降低了脑组织中IL-1β、TNFα、ET₁和NO₂的水平。与正常体温组相比，低温还降低了血清中LDH、AST、CK和CK-BB的水平（p < 0.05或p < 0.01）。持续30分钟的低温延缓了脑组织中这些氨基酸和5-HT水平的下降以及5-HIAA水平的升高（p < 0.05），但与正常体温缺血组相比，未能影响脑组织中IL-1β、TNFα、ET₁和NO₂的水平以及血清中LDH、AST、CK和CK-BB的含量（p > 0.05）。
缺血后轻度脑低温可显著抑制缺血组织中氨基酸、单胺类神经递质的过度释放和炎症反应。它还能稳定细胞膜的功能，这与轻度低温的脑保护机制有关。这些结果表明，为获得神经保护作用，应在缺血后立即应用轻度低温并持续超过60分钟。
