Protective Effect Of Local Mild Hypothermia On The Brain Against Ischemia-Reperfusion Injury In Rats

Objective: To investigate the protective effect of Local mild hypothermia on the brain against ischemia-reperfusion (I/R) injury in rats and the underlying mechanism.MethodsThirty-two male Sprague - Dawley rats weighing 200-250g were randomly divided into 4 groups (n = 8 each): (S) sham operating group; (I/R) ischemia–reperfusion group; (H) mild hypothermia+ I/R group and (5-HD) 5-HD +mild hypothermia + I/R group. The model of cerebral ischemia–reperfusion injury in rats was induced by occlusion of bilateral common carotid arteries and basilar artery for 10 min and then reopening them for 6 h .(1)S group : bilateral common carotid arteries and basilar artery were not occluded, other conditions were same with I/R group .(2)I/R group : three vessels were occluded for 10 min and then reopening them for 6 h .(3)H group and 5-HD + H group : the rats were provided 3 h local mild hypothermia after the injection of 10℃normal saline 3.5 ml via femoral vein at the time of reperfusion, combing with 60 w incandescent lamp shotting body , pieces of ice surrounding head. monitoring periost temperature and rectum temperature , 1 min after reperfusion periost temperature began to drop in , then maintained at 32-34℃during the hypothermia . Rectum temperature dropped in too , after 20 min went up to normothermia under shotting of incandescent lamp . Hypothermia maintained for 3 h .then rewarming slowly .(4) 5-HD + H group : 10 mg/kg 5-HD was injected into abdominal cavity in 30 min before cerebral ischemia . Rats of other groups were injected equal volume normal saline . When the experiment was completed , the vein blood samples were taken from internal jugular vein of rats , Serum S100B protein levels were analyzed with ELISA. Then Animals were decapitated and anterior lobe of the right brain was removed for light microscopic and ultrastrucrure examination . Brain water content was determined by dry-wet weight method on the left . The other brain tissue was used to measure the content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity.Results1 The activity of SODCompared with S group , I/R group SOD activity significantly increased (P < 0.05 ) . Compared with I/R group , H group SOD activity decreased ( P < 0.05 ) . 5-HD + H group SOD activity were between H group and I/R group .There were significant differences among them ( P < 0.05 ).2 Serum S100B protein level, brain water content and content of malondialdehyde (MDA)Compared with S group , I/R group Serum S100B protein level, brain water content and content of malondialdehyde (MDA) were increased (P < 0.05) . Compared with I/R group , H group Serum S100B protein level, brain water content and content of malondialdehyde (MDA) were significantly decreased (P < 0.05 ). 5-HD + H group Serum S100B protein levels, brain water content and content of malondialdehyde (MDA) were between H group and I/R group . There were significant differences among them ( P < 0.05 ).3 Results of light microscope and electron microscopeH group injury degree of the cortex neurons in rats was ameliorated effectively. 5-HD + H group injury degree was between H group and I/R group. H group ameliorated significantly .ConclusionLocal mild hypothermia has protective effect on the brain against I/R injury . Activation of KATP channel is involved in the mechanism .