Heating of the brain to maintain normothermia during ischemia aggravates brain injury in the rat.
During brain ischemia temperature spontaneously declines. In animal experiments this decline is frequently prevented by stabilizing the temperature at the pre-ischemic level, using an external heat source. The present study examines whether this procedure influences the severity of ischemic injury. Wistar rats were submitted to 30-min four-vessel occlusion followed by 7 days recirculation. During ischemia and the 1st h of recirculation various systemic and electrophysiological variables were recorded. Seven days after the ischemia brains were perfusion-fixed for light microscopical examination. Three brain temperature profiles were compared: spontaneous decline of brain temperature during ischemia from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5); constant brain temperature of 30 degrees C induced by selective head cooling (induced hypothermia; n = 5); and constant brain temperature of 36 degrees C induced by selective head heating (normothermia; n = 5). Core temperature was maintained constant at 37 degrees C in all groups. In spontaneous hypothermia, 19% of CA1 neurons survived after 30-min ischemia. Induced hypothermia significantly increased this percentage to 69% (P < 0.05); maintenance of brain temperature at normothermia decreased neuronal survival to 1%. Normothermia also led to morphological injury outside the vulnerable regions, an increase in mortality, marked loss of body weight and a prolongation of the electroencephalographic suppression. These findings demonstrate that stabilizing brain temperature at a constant normothermic level by an external heart source introduces an aggravating pathological element that may interfere in an unpredictable way with the manifestation or treatment of ischemic injury.
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Köln, Germany.
T
T
Miyazawa
P
P
Bonnekoh
R
R
Widmann
K A
KA
Hossmann
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002339:Carotid Arteries / Q000502:physiology; D004569:Electroencephalography; D006358:Hot Temperature; D008297:Male; D016548:Prosencephalon / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016707:Tissue Fixation