HIBERNATION IN-GROUND SQUIRRELS INDUCES STATE AND SPECIES-SPECIFIC TOLERANCE TO HYPOXIA AND AGLYCEMIA - AN IN-VITRO STUDY IN HIPPOCAMPAL SLICES

Hibernation in mammals is associated with a regulated depression or gl obal cellular functions accompanied by reductions of cerebral blood fl ow that would render the brain profoundly ischemic under normal condit ions, Homeostatic control is preserved, however, and brain damage does not occur, We investigated the possibility that hibernation not only confers tolerance to profound hypothermia, but also to hypo?iia and ag lycemia independent of temperature, Hippocampal slices from ground squ irrels Citellus tidecemlineatus in both the active and hibernating sta tes and from rats were subjected to in vitro hypoxia and aglycemia at incubation temperatures of 36 degrees C, 20 degrees C, and 7 degrees C , and evaluated histologically. A binary bioassay was used to determin e the duration of hypoxia/aglycemia tolerated in each group. At all te mperatures. slices from hibernating animals were most tolerant compare d with both active squirrels and rats. Slices from active ground squir rels were more tolerant than rat at 20 degrees C and 7 degrees C but n ot at 36 degrees C indicating a species-specific difference that becom es manifest at lower temperatures. These results indicate that hiberna tion is associated not only with tolerance to profound hypothermia but also to deprivation of oxygen and glucose. Because tolerance was alre ady demonstrable at the shortest duration of hibernation studied, rapi d therapeutic induction of a similar state mau be possible, Therefore, identification of the regulatory mechanisms underlying this tolerance may lead to novel neuroprotective strategies.