Early Transient Mild Hypothermia Attenuates Neurologic Deficits and Brain Damage After Experimental Subarachnoid Hemorrhage in Rats.

Abstract

Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. Twenty male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34°C) or served as controls by continuous maintenance of normothermia (37.0°C). Mean arterial blood pressure, intracranial pressure, and local cerebral blood flow over both hemispheres were continuously measured. Neurologic assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin-eosin and caspase-3 staining. By a slight increase of mean arterial blood pressure in the cooling phase and a significant reduction of intracranial pressure, hypothermia improved cerebral perfusion pressure in the first 60 minutes after SAH. Accordingly, a trend to increased cerebral blood flow was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared with normothermic controls. The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH.