Review articleHibernation-like neuroprotection in stroke by attenuating brain metabolic dysfunction

•Artificial hibernation (or a 'hibernation-like state') has been identified as a potential therapy for ischemic stroke.•Three methods of artificial hibernation induction are reviewed: therapeutic hypothermia, phenothiazine drugs, and ethanol.•These three methods have unique, but related, therapeutic effects on the pathophysiology of ischemic stroke.

Many mammalian species naturally undergo hibernation, a process that is associated with drastic changes in metabolism and systemic physiology. Their ability to retain an undamaged central nervous system during severely reduced cerebral blood flow has been studied for possible therapeutic application in human ischemic stroke. By inducing a less extreme 'hibernation-like' state, it has been hypothesized that similar neuroprotective effects reduce ischemia-mediated tissue damage in stroke patients. This manuscript includes reviews and evaluations of: (1) true hibernation, (2) hibernation-like state and its neuroprotective characteristics, (3) the preclinical and clinical methods for induction of artificial hibernation (i.e., therapeutic hypothermia, phenothiazine drugs, and ethanol), and (4) the mechanisms by which cerebral ischemia leads to tissue damage and how the above-mentioned induction methods function to inhibit those processes.