Barone F C, Feuerstein G Z, White R F
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Neurosci Biobehav Rev. 1997 Jan;21(1):31-44. doi: 10.1016/0149-7634(95)00080-1.
A review of the effects of reducing brain temperature on ischemic brain injury is presented together with original data describing the systematic evaluation of the effects of brain cooling on brain injury produced by transient focal ischemia. Male spontaneously hypertensive rate were subjected to transient middle cerebral artery occlusion (TMCAO; 80, 120 or 160 min) followed by 24 h of reperfusion. During TMCAO, the exposed skull was bathed with isotonic saline at various temperatures to control skull and deeper brain temperatures. Rectal temperature was always constant at 37 degrees C. Initial studies indicated that skull temperature was decreased significantly (i.e. to 32-33 degrees C) just as a consequence of surgical exposure of the artery. Subsequent studies indicated that maintaining skull temperature at 37 degrees C compared to 32 degrees C significantly (p < 0.05) increased the infarct size following 120 or 160 min TMCAO. In other studies, 80 min TMCAO was held constant, but deeper brain temperature could be varied by regulating skull temperature at different levels. At 36-38 degrees C brain temperature, infarct volumes of 102 +/- 10 to 91 +/- 9 mm3 occurred following TMCAO. However, at a brain temperature of 34 degrees C, a significantly (p < 0.05) reduced infarct volume of 37 +/- 10 mm3 was observed. Absolutely no brain infarction was observed if the brain was cooled to 29 degrees C during TMCAO. Middle cerebral artery exposure and maintaining brain temperature at 37 degrees C without artery occlusion did not produce any cerebral injury. These data indicated the importance of controlling brain temperature in cerebral ischemia and that reducing brain temperature during ischemia produces a brain temperature-related decrease in focal ischemic damage. Brain cooling of 3 degrees C and 8 degrees C can provide dramatic and complete, respectively, neuroprotection from transient focal ischemia. Multiple mechanisms for reduced brain temperature-induced neuroprotection have been identified and include reduced metabolic rate and energy depletion, decreased excitatory transmitter release, reduced alterations in ion flux, and reduced vascular permeability, edema, and blood-brain barrier disruption. Cerebral hypothermia is clearly the most potent therapeutic approach to reducing experimental ischemic brain injury identified to date, and this is emphasized by the present data which demonstrate complete neuroprotection in transient focal stroke. Certainly all available information warrants the evaluation of brain cooling for potential implementation in the treatment of human stroke.
本文综述了降低脑温对缺血性脑损伤的影响，并给出了原始数据，这些数据描述了对脑冷却对短暂性局灶性缺血所致脑损伤影响的系统评估。雄性自发性高血压大鼠接受短暂性大脑中动脉闭塞（TMCAO，80、120或160分钟），随后再灌注24小时。在TMCAO期间，将暴露的颅骨用不同温度的等渗盐水冲洗，以控制颅骨和更深层脑的温度。直肠温度始终保持在37摄氏度。初步研究表明，仅由于动脉的手术暴露，颅骨温度就显著降低（即降至32 - 33摄氏度）。随后的研究表明，与32摄氏度相比，在120或160分钟TMCAO后，将颅骨温度维持在37摄氏度会显著（p < 0.05）增加梗死面积。在其他研究中，80分钟TMCAO保持不变，但可通过在不同水平调节颅骨温度来改变更深层脑的温度。在36 - 38摄氏度脑温下，TMCAO后梗死体积为102±10至91±9立方毫米。然而，在34摄氏度脑温下，观察到梗死体积显著（p < 0.05）减小，为37±10立方毫米。如果在TMCAO期间将脑冷却至29摄氏度，则绝对没有观察到脑梗死。暴露大脑中动脉并在不闭塞动脉的情况下将脑温维持在37摄氏度不会产生任何脑损伤。这些数据表明了在脑缺血中控制脑温的重要性，并且缺血期间降低脑温会使局灶性缺血损伤随脑温降低而减少。脑冷却3摄氏度和8摄氏度分别可以为短暂性局灶性缺血提供显著和完全的神经保护。已经确定了降低脑温诱导神经保护的多种机制，包括降低代谢率和能量消耗、减少兴奋性递质释放、减少离子通量改变以及降低血管通透性、水肿和血脑屏障破坏。脑低温显然是迄今为止确定的减轻实验性缺血性脑损伤最有效的治疗方法，本数据强调了这一点，这些数据表明在短暂性局灶性中风中可实现完全的神经保护。当然，所有现有信息都支持对脑冷却进行评估，以探讨其在人类中风治疗中的潜在应用。
