Nathaniel Thomas I
Center for Natural and Health Sciences, Marywood University, 2300 Adams Avenue, Scranton, PA 18509, USA.
Int J Stroke. 2008 May;3(2):98-104. doi: 10.1111/j.1747-4949.2008.00186.x.
Hypoxic-ischemic brain injury in the perinatal period is a major cause of chronic disability and acute mortality in newborns. Despite numerous therapeutic strategies that reduce hypoxia-ischemia-induced damage in different experimental animal models, most of them have failed to translate to clinical therapies. This challenge calls for an urgent need to explore novel approaches to develop effective therapies for the clinical management of perinatal hypoxia-ischemia brain injury. This review focuses on studies that investigate neuroprotective related events during mammalian hibernation, characterized by dramatic reductions in several parameters including body temperature, oxygen consumption and heart rate, such that it is difficult to tell if the hibernating animal is dead or alive. The first part of this article reviews the mechanisms of metabolic suppression related events during hibernation. In the second part, hypoxic-ischemic events in the perinatal brain are discussed, and in turn, contrasted with brains experiencing metabolic suppression during mammalian hibernation. In the last part of this article, the diverse neuroprotective adaptations of hibernators and the mechanisms that might be involved in mammalian hibernation, and how they could in turn, contribute to neurprotection during perinatal hypoxia-ischemia related injuries are discussed. This article appraises the novel idea that knowledge of the central mechanisms involved in the regulatory metabolic suppression, during which; hibernators switch themselves off without dissolving their brains could represent brain neuroprotective strategy for the clinical management of perinatal hypoxia-ischemia brain injuries in newborns.
围生期缺氧缺血性脑损伤是新生儿慢性残疾和急性死亡的主要原因。尽管有许多治疗策略可在不同实验动物模型中减少缺氧缺血性损伤，但其中大多数未能转化为临床治疗方法。这一挑战迫切需要探索新的方法来开发有效的疗法，用于围生期缺氧缺血性脑损伤的临床管理。本综述聚焦于研究哺乳动物冬眠期间与神经保护相关的事件，其特征是包括体温、耗氧量和心率在内的多个参数显著降低，以至于很难判断冬眠动物是死是活。本文第一部分综述了冬眠期间代谢抑制相关事件的机制。第二部分讨论了围生期脑的缺氧缺血事件，并将其与哺乳动物冬眠期间经历代谢抑制的脑进行对比。在本文最后一部分，讨论了冬眠动物多样的神经保护适应性以及可能参与哺乳动物冬眠的机制，以及它们如何反过来有助于围生期缺氧缺血相关损伤期间的神经保护。本文评估了一个新观点，即了解参与调节代谢抑制的核心机制，在此期间冬眠动物在不溶解大脑的情况下自我关闭，这可能代表了一种针对新生儿围生期缺氧缺血性脑损伤临床管理的脑保护策略。
