Maier C M, Sun G H, Kunis D, Yenari M A, Steinberg G K
Department of Neurosurgery, Stanford Stroke Center, Stanford University Medical Center, California 94305, USA.
J Neurosurg. 2001 Jan;94(1):90-6. doi: 10.3171/jns.2001.94.1.0090.
The goals of this study were to determine the effects of delaying induction of mild hypothermia (33 degrees C) after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over time.
In the first study, rats underwent 2 hours of middle cerebral artery (MCA) occlusion. Animals in one group were maintained under normothermic conditions (N group, 23 rats) throughout the period of ischemia and reperfusion. Rats in four additional groups were exposed to 2 hours of hypothermia, which commenced at ischemia onset (H0 group, 11 rats) or with delays of 90 (H90 group, 10 rats), 120 (H120 group, 10 rats), or 180 (H180 group, five rats) minutes, and allowed to survive for 3 days. In the second study, animals underwent 1.5 hours of MCA occlusion and were maintained under normothermic (48 rats) or hypothermic (44 rats) conditions during the ischemia period, after which they survived for 3 days, 1 week, or 2 months. All animals were evaluated for neurological findings at 24 hours and 48 hours postischemia and before they were killed. Regions of infarct were determined by examining hematoxylin and eosinstained brain slices obtained at six coronal levels.
Mild hypothermia conferred significant degrees of neuroprotection in terms of survival, behavioral deficits, and histopathological changes, even when its induction was delayed by 120 minutes after onset of MCA occlusion (p < 0.05) compared with normothermic conditions. Furthermore, the neuroprotective effect of mild hypothermia (2-hour duration) that was induced during the ischemia period was sustained over 2 months. These studies lend further support to the use of mild hypothermia in the treatment of stroke.
本研究的目的是确定短暂性局灶性脑缺血后延迟诱导轻度低温（33摄氏度）的效果，并确定缺血期诱导的轻度低温的神经保护作用是否随时间持续存在。
在第一项研究中，大鼠经历了2小时的大脑中动脉（MCA）闭塞。一组动物在整个缺血和再灌注期间维持在常温条件下（N组，23只大鼠）。另外四组大鼠暴露于2小时的低温环境，低温在缺血开始时开始（H0组，11只大鼠）或延迟90分钟（H90组，10只大鼠）、120分钟（H120组，10只大鼠）或180分钟（H180组，5只大鼠），并存活3天。在第二项研究中，动物经历了1.5小时的MCA闭塞，并在缺血期维持在常温（48只大鼠）或低温（44只大鼠）条件下，之后存活3天、1周或2个月。所有动物在缺血后24小时和48小时以及处死前进行神经学检查。通过检查在六个冠状层面获得的苏木精和伊红染色的脑切片来确定梗死区域。
即使在MCA闭塞开始后120分钟延迟诱导轻度低温，与常温条件相比，在生存、行为缺陷和组织病理学变化方面，轻度低温仍具有显著程度的神经保护作用（p<0.05）。此外，缺血期诱导的轻度低温（持续2小时）的神经保护作用持续了2个月。这些研究进一步支持了轻度低温在中风治疗中的应用。
