Experimental Study On The Preconditioning Therapy For Protection Against Focal Ischemia In Rats By Mild Hypothermia

Purpose: The blood flow should often be occluded during neurosurgery in dealing with brain vascular diseases, resulting in brain ischemia, which can be predicted before operation. There has been no effective and affirmative measure to extend the duration of brain ischemia so far. It has been proved that mild hypothermia has protective effect on ischemic brain damage, but there is no last word on the therapeutic time window and time limit of mild hypothermia applying. The present study is designed to determine whether mild hypothermia initiated immediately after the onset of focal brain ischemia improves neurological outcome, reduces infarct volume and protects against ischemic neuronal damage in different regions of brain, according to different duration of ischemia, and in addition, to study the relationship between the effect of mild hypothermia and the duration of brain ischemia. Methods: Reversible middle cerebral artery occlusion (MCAO) was induced as described by Zea longa et aL and modified by Ludmila Belayev et al, employing a intraluminal suture. Spregue-Dawley rats were assigned randomly to one of six groups (n=7) as follows: 1 hr MCAO-normothermic group, 1 hr MCAO-mild hypothermia group; 2 hr MCAO-normothermic group, 2 hr MCAO-mild hypothermia group; 3 hr MCAO-normothermic group and 3 hr MCAO-mild hypothermia group. The rectal temperature of the normothermic group was maintained at 37.5℃ during ischemia. The rectal temperature of the mild hypothermia group was maintained at 33-34℃ before the onset of ischemia and rewarming began immediately after the onset of reperfusion. Neurological examinations were performed 4 and 8 hours after the onset of occlusion and then daily until sacrifice. All surviving rats were killed 72 hours after the onset of occlusion and then, the infarct area was determined. Four regions, included the CAl and CA3 sectors of the hippocampus, parietal cortex and striatum, were examined semiquantitatively for histological evidence of injury. Results: 8 hours after the onset of occlusion, applying hypothermia can improve the neurological outcome significantly versus 1 hr MCAO group and 2 hr MCAO under normothermic condition. There was no significant different between the 3 hr MCAO groups. The infarct volume of 1 hr MCAO and 2 hr MCAO-hypothermic groups were significantly smaller (74±10mm~3 and 142±3mm~3)(SEM) than that of normothermic groups respectively(132±15mm~3 and 221±16mm~3,P<0.05). There was no significant different (217±36mm~3versus199±25mm~3,P>0.05) between the 3 hr MCAO-normothermic and hypothermic group. In 1 hr MCAO and 2 hr MCAO groups, mild hypothermia significantly reduced the percentage of necrotic neurons in the CA1 and CA3 sectors of the hippocampus, parietal cortex and striatum compared with the normothermic groups accordingly by seniiquantative examination(PO.05) There is a correlation among the improvement of neurological outcome, infarct volume and severity of neuronal damage after the onset of occlusion. The more gently the neuronal damage was, the smaller the infarct volume was and the more the neurological outcome was improved. Conclusion:...