Brain Cooling During Transient Focal Ischemia Provides Complete Neuroprotection

Abstract BARONE, F.C., G.Z. FEUERSTEIN AND R.F. WHITE. Brain cooling during transient focal ischemia provides complete neuroprotection . NEUROSCI BIOBEHAV REV 21 (1) 31–44, 1997.—A review of the effects of reducing brain temperature on ischemic brain injury is presented together with original data describing the systematic evaluation of the effects of brain cooling on brain injury produced by transient focal ischemia. Male spontaneously hypertensive rate were subjected to transient middle cerebral artery occlusion (TMCAO; 80, 120 or 160 min) followed by 24 h of reperfusion. During TMCAO, the exposed skull was bathed with isotonic saline at various temperatures to control skull and deeper brain temperatures. Rectal temperature was always constant at 37°C. Initial studies indicated that skull temperature was decreased significantly (i.e. to 32–33°C) just as a consequence of surgical exposure of the artery. Subsequent studies indicated that maintaining skull temperature at 37°C compared to 32°C significantly ( p 3 occurred following TMCAO. However, at a brain temperature of 34°C, a significantly ( p 3 was observed. Absolutely no brain infarction was observed if the brain was cooled to 29°C during TMCAO. Middle cerebral artery exposure and maintaining brain temperature at 37°C without artery occlusion did not produce any cerebral injury. These data indicate the importance of controlling brain temperature in cerebral ischemia and that reducing brain temperature during ischemia produces a brain temperature-related decrease in focal ischemic damage. Brain cooling of 3°C and 8°C can provide dramatic and complete, respectively, neuroprotection from transient focal ischemia. Multiple mechanisms for reduced brain temperature-induced neuroprotection have been identified and include reduced metabolic rate and energy depletion, decreased excitatory transmitter release, reduced alterations in ion flux, and reduced vascular permeability, edema, and blood-brain barrier disruption. Cerebral hypothermia is clearly the most potent therapeutic approach to reducing experimental ischemic brain injury identified to date, and this is emphasized by the present data which demonstrate complete neuroprotection in transient focal stroke. Certainly all available information warrants the evaluation of brain cooling for potential implementation in the treatment of human stroke. Copyright © 1996 Elsevier Science Ltd.