Tang Xian N, Liu Liping, Yenari Midori A
Department of Neurology, University of California, San Francisco & San Francisco Veterans Administration Medical Center, San Francisco, California 94121, USA.
J Neurotrauma. 2009 Mar;26(3):325-31. doi: 10.1089/neu.2008.0594.
Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have suffered cardiac arrest and in some pediatric populations suffering hypoxic brain insults. However, a review of the literature has demonstrated that in order to appreciate the maximum benefits of hypothermia, brain cooling needs to begin soon after the insult, maintained for relatively long period periods of time, and, in the case of ischemic stroke, should be applied in conjunction with the re-establishment of cerebral perfusion. Translating this to the clinical arena can be challenging, especially rapid cooling and the re-establishment of perfusion. The addition of a second neuroprotectant could potentially (1) enhance overall protection, (2) prolong the temporal therapeutic window for hypothermia, or (3) provide protection where hypothermic treatment is only transient. Combination therapies resulting in recanalization following ischemic stroke would improve the likelihood of a good outcome, as the experimental literature suggests more consistent neuroprotection against ischemia with reperfusion, than ischemia without. Since recombinant tissue plasiminogen activator (rt-PA) is the only FDA approved treatment for acute ischemic stroke, and acts to recanalize occluded vessels, it is an obvious initial strategy to combine with hypothermia. However, the effects of thrombolytics are also temperature dependent, and the risk of hemorrhage is significant. The experimental data nevertheless seem to favor a combinatorial approach. Thus, in order to apply hypothermia to a broader range of patients, combination strategies should be further investigated.
轻度低温在实验室中是一种公认的神经保护剂，在多个实验室和脑损伤模型中均显示出显著且一致的效果。在临床层面，轻度低温已在心脏骤停患者以及一些遭受缺氧性脑损伤的儿科患者中显示出益处。然而，文献综述表明，为了充分发挥低温的最大益处，脑部降温需要在损伤后尽快开始，并持续较长时间，而且对于缺血性中风患者，应在恢复脑灌注的同时应用。将其应用于临床领域可能具有挑战性，尤其是快速降温和恢复灌注。添加第二种神经保护剂可能会（1）增强整体保护作用，（2）延长低温治疗的时间窗，或者（3）在低温治疗只是短暂性的情况下提供保护。缺血性中风后实现再通的联合疗法将提高获得良好预后的可能性，因为实验文献表明，与单纯缺血相比，再灌注对缺血的神经保护作用更一致。由于重组组织型纤溶酶原激活剂（rt-PA）是美国食品药品监督管理局（FDA）批准的唯一用于急性缺血性中风的治疗药物，其作用是使闭塞血管再通，因此将其与低温联合是一种明显的初始策略。然而，溶栓药物的效果也取决于温度，且出血风险很大。尽管如此，实验数据似乎支持联合治疗方法。因此，为了将低温应用于更广泛的患者群体，应进一步研究联合策略。
