Insights into cytoprotection from ground squirrel hibernation, a natural model of tolerance to profound brain oligaemia.

Progression of acute ischaemic brain damage is complex and multifactorial. Also, evidence suggests that participating molecules and signal transduction pathways can function differently in different cellular contexts. Hibernation torpor, a model of natural tolerance to profoundly reduced blood flow and oxygen delivery to brain, along with models of induced ischaemic tolerance can guide efforts to identify cytoprotective mechanisms that are multifactorial and that target multiple mechanisms in multiple cellular contexts. Post-translational modification of proteins by conjugation with the SUMO (small ubiquitin-related modifier) is massively increased in hibernation and may be such a mechanism.