Local Cerebral Blood Flow during Hibernation, a Model of Natural Tolerance to “Cerebral Ischemia”

Abstract

The breakdown of cellular homeostasis and progressive neuronal destruction in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a physiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduced oxygen availability and to resist activation of self-destructive processes, i.e., mammalian hibernation. Ground squirrels (Spermophilus tridecemlineatus) were chronically implanted with arterial and venous catheters and telemetry devices for electroencephalography, electrocardiography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5°C. Entrance into hibernation was characterized by a drop in heart rate followed by a gradual decline in body temperature and an isoelectric electroencephalogram. Cold-adapted active animals that were not hibernating served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [14C]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 animals aroused from hibernation. Hibernation appears to be actively regulated, and hormonal factors may be involved. The identification and characterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive effects of ischemia may enable us to prevent or minimize the loss of homeostatic control during and after cerebral ischemia in other species.