Maier C M, Ahern K v, Cheng M L, Lee J E, Yenari M A, Steinberg G K
Departments of Neurosurgery, Stanford Stroke Center, Stanford University, Stanford, Calif.
Stroke. 1998 Oct;29(10):2171-80. doi: 10.1161/01.str.29.10.2171.
Mild hypothermia is possibly the single most effective method of cerebroprotection developed to date. However, many questions regarding mild hypothermia remain to be addressed before its potential implementation in the treatment of human stroke. Here we report the results of 2 studies designed to determine the optimal depth and duration of mild hypothermia in focal stroke and its effects on infarct size, neurological outcome, programmed cell death, and inflammation.
Rats underwent a 2-hour occlusion of the left middle cerebral artery. In the first study (I) animals were kept (intraischemically) at either 37 degreesC (n=8), 33 degreesC (n=8), or 30 degreesC (n=8). Study II consisted of 4 groups: (1) controls (37 degreesC, n=10), (2) 30 minutes of hypothermia started at ischemic onset (33 degreesC, n=9), (3)1 hour (33 degreesC, n=8), and (4) 2 hours (33 degreesC, n=8). Brain temperature was measured by a thermocouple probe placed in the contralateral cortex. After suture removal, all animals were rewarmed and reperfused for 22 hours (I) or 70 hours (II).
Mild hypothermia to 33 degreesC or 30 degreesC was neuroprotective (17+/-7% and 27+/-6%, respectively) relative to controls (53+/-8%, P<0.02), but 33 degreesC was better tolerated and recovery from anesthesia was faster. The neurological score of hypothermic animals was significantly better than that of controls (I & II) at both 24 and 72 hours postischemia except for the 30-minute group (II), which showed no improvement. In Study II, 2 hours of hypothermia reduced injury by 59%, 1 hour reduced injury by 84% whereas 30 minutes did not reduce injury. Normalized for infarct size, 2 hours of mild hypothermia decreased neutrophil accumulation by 57% whereas both 1 hour and 30 minutes had no effect. At 72 hours, 1 and 2 hours of mild hypothermia decreased transferase dUTP nick-end labeling (TUNEL) staining by 78% and 99%, respectively, and 30 minutes of hypothermia had no effect.
Intraischemic mild hypothermia must be maintained for 1 to 2 hours to obtain optimal neuroprotection against ischemic cell death due to necrosis and apoptosis.
轻度低温可能是目前已开发出的最有效的脑保护单一方法。然而，在将其潜在应用于人类中风治疗之前，关于轻度低温仍有许多问题有待解决。在此，我们报告两项研究的结果，旨在确定局灶性中风中轻度低温的最佳深度和持续时间及其对梗死体积、神经功能结局、程序性细胞死亡和炎症的影响。
大鼠接受左侧大脑中动脉2小时闭塞。在第一项研究（I）中，动物在缺血期间分别维持在37℃（n = 8）、33℃（n = 8）或30℃（n = 8）。研究II包括4组：（1）对照组（37℃，n = 10），（2）缺血开始时开始30分钟低温（33℃，n = 9），（3）1小时（33℃，n = 8），和（4）2小时（33℃，n = 8）。通过置于对侧皮质的热电偶探头测量脑温。移除缝合线后，所有动物复温并再灌注22小时（I）或70小时（II）。
相对于对照组（53±8%），轻度低温至33℃或30℃具有神经保护作用（分别为17±7%和27±6%，P<0.02），但33℃耐受性更好且麻醉恢复更快。除30分钟组（II）无改善外，低温动物在缺血后24小时和72小时的神经评分均显著优于对照组（I和II）。在研究II中，2小时低温使损伤减少59%，1小时低温使损伤减少84%，而30分钟低温未减少损伤。以梗死体积标准化后，2小时轻度低温使中性粒细胞积聚减少57%，而1小时和30分钟均无影响。在72小时时，1小时和2小时轻度低温分别使转移酶dUTP缺口末端标记（TUNEL）染色减少78%和99%，30分钟低温无影响。
缺血期间必须维持轻度低温1至2小时，以获得针对因坏死和凋亡导致的缺血性细胞死亡的最佳神经保护作用。
