Hibernation in mammals is characterised by a marked decrease in body temperature and a dramatic suppression of metabolism. In addition, despite experiencing a reduced cardiac output that would normally cause profound cerebral ischaemia, hibernating animals display robust neuroprotection. However, whether the reduced susceptibility to neural injury displayed by hibernators is attributable to an innate factor, or to the physiologic changes that accompany hibernation, remains uncertain. To help clarify the nature of the ischaemic tolerance displayed by hibernators, the current study examined hippocampal slices from rodents not capable of hibernation (rat) and rodents that could undergo hibernation (hamsters), but were active immediately prior to slice preparation. Slices from each species were subjected to oxygen-glucose deprivation (OGD; a commonly used in vitro model of ischaemia), and their viability examined after a recovery period. Although OGD reduced plasma membrane integrity in each species, rat-derived slices displayed a nearly threefold greater degree of effect. In addition, only slices harvested from rats showed reductions in synaptic mitochondrial function. While the improved ischaemic tolerance displayed by euthermic hamster brain slices maintained at a physiological temperature suggests an intrinsic, protection-related variable, the synaptic level of the GluN1 subunit (which is required to form functional NMDA receptors) was not found to be different between the two species. Further work is needed to improve understanding of the molecular mechanisms underlying the intrinsic injury tolerance of hibernator brain, which should help provide inspiration for new approaches to neuroprotection.