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COMPARATIVE AND EVOLUTIONARY PHYSIOLOGY

Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels

¹Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks; and ²Institute of Pathology, ³Department of Neurology, Case Western Reserve University, Cleveland, Ohio

Submitted 13 April 2005 ; accepted in final form 20 June 2005

Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O₂ saturation (SO₂), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O₂ tension (Pa_O2) and SO₂ are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1 accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low SO₂ and accumulation of HIF-1 and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.

torpor; ischemia; stroke; Spermophilus parryii; reperfusion; inflammation; oxidative stress

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