Brain-regulated metabolic suppression during hibernation: a neuroprotective mechanism for perinatal hypoxia-ischemia.

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.