LOCAL CEREBRAL BLOOD-FLOW DURING HIBERNATION, A MODEL OF NATURAL TOLERANCE TO CEREBRAL-ISCHEMIA

The breakdown of cellular homeostasis and progressive neuronal destruc tion in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a ph ysiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduce d oxygen availability and to resist activation of self-destructive pro cesses, i.e., mammalian hibernation. Ground squirrels (Spermophilus tr idecemlineatus) were chronically implanted with arterial and ve nous c atheters and telemetry devices for electroencephalography, electrocard iography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5 degrees C. Entrance into hibernation was characterized by a drop in heart rate fo llowed by a gradual decline in body temperature and an isoelectric ele ctroencephalogram. Cold-adapted active animals that were not hibernati ng served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [C-14]iodoantipyrine method. Mean (+/ - SD) mass-weighted CBF in the brain as a whole was 62 +/- 16 ml/100 g /min (n = 4) in the control group but was reduced to ischemic levels, 7 +/- 4 ml/100 g/min (n = 4), in the hibernating animals (p < 0.001). No neuropathological changes were found in similarly hibernating anima ls aroused from hibernation. Hibernation appears to be actively regula ted, and hormonal factors may be involved. The identification and char acterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive e ffects of ischemia may enable us to prevent or minimize the loss of ho meostatic control during and after cerebral ischemia in other species.