Summary
The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37°C) or moderately hypothermic (33°C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33°C,P<0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P<0.01) when halothane, but not isoflurane was used. Damage to CA1 neurons was mild in both groups with halothane, but slightly less frequent (P< 0.05) in the hypothermic group, in which the majority of animals showed no damage. No protection of hypothermia was seen in the animals with isoflurane anesthesia. Furthermore, with isoflurane, more damaged CA1 cells were seen in the normothermic situation as compared to when halothane was used (P<0.01). In contrast, damage to the tip of the dentate gyrus was remarkedely resistant to hypothermia, with the majority of animals showing the same degree of damage as the normothermic ones irrespective of the anesthetic agent used. In summary, hypothermia seemed to have only a partial protective effect on the development of hypoglycemic brain damage, the effects differing between regions previously described to be selectively vulnerable to hypoglycemia, and also differing when halothane or isoflurane were used as anesthetic agents. While long-term survival was achieved with the use of isoflurane, the protective effect of hypothermia seemed to be lost.
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Supported by the Swedish Medical Research Council (grants no. 14X-263 and 12X-7123), the National Institutes of Health of the United States Public Health Service (grant no. 5 R01 NS-07838) and the Medical Faculty, Lund University
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Agardh, C.D., Smith, M.L. & Siesjö, B.K. The influence of hypothermia on hypoglycemia-induced brain damage in the rat. Acta Neuropathol 83, 379–385 (1992). https://doi.org/10.1007/BF00713529
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DOI: https://doi.org/10.1007/BF00713529