Controlled whole-body cooling has been used since the 1950s to protect the brain from injury where cerebral blood flow is reduced. Therapeutic hypothermia has been used successfully during heart surgery, following cardiac arrest and with varied success in other instances of reduced blood flow to the brain. However, why reduced temperature is beneficial is largely unknown. Here we review the use of therapeutic hypothermia with a view to understanding the underlying biology contributing to the phenomenon. Interestingly, the benefits of cooling have recently been extended to treatment of chronic neurodegenerative diseases in two mouse models. Concurrently studies have demonstrated the importance of the regulation of protein synthesis, translation, to the cooling response, which is also emerging as a targetable process in neurodegeneration. Through these studies the potential importance of the rewarming process following cooling is also beginning to emerge. Altogether, these lines of research present new opportunities to manipulate cooling pathways for therapeutic gain.

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