Neuroprotective Effect Of Postconditioning On Thrombotic Cerebral Ischemic Injury In Tree Shrews

Objective:To observe the influences of ischemia and pharmacologic postconditioning on changes of cerebral cortex water content, cerebral blood flow, infarct size and hippocampal ultrastructural, compare the neuroprotective effect of ischemic and pharmacologic postconditioning, and confirm the possible neuroprotective mechanisms of this two postconditioning on reducing thrombotic cerebral ischemic injury in tree shrews.Methods:Thrombotic cerebral ischemia in tree shrews was induced by photochemistry. Ischemic postconditioning was performed at 4h after light expose; right common carotid artery was occluded and perfusion for 5min alternatively for 3 circles.0.5%histidine (lml/kg) was injected into the sublingual vein as pharmacologic postconditioning. Elliott dry-wet weight method was used to detect the brain water content of local cortex, 2,3,5-triphenyl-tetrazolium chloride(TTC) stain was used to show the brain infarct size, Laser Doppler to detect regional cerebral blood flow(rCBF) of local cortex, and the ultrastructural changes in CA1 area of hippocampus in different groups were observed under the electronmicroscope.Results:At 24h The brain water content in pharmacologic postconditioning with histidine(Is+His) group were significantly reduced than that in the cerebral ischemia group (P<0.01). The rCBF in Is+His group were significantly increased than the cerebral ischemia group (P<0.01) at 4h,12h and 24h. The infarct size in Is+His group were significantly lessen than cerebral ischemia group at 12h and 24h (P<0.01). The brain water content in ischemic postconditioning group were decreased than the cerebral ischemia group significantly at 24h(P<0.01). The rCBF in ischemic postconditioning group were enhanced than cerebral ischemia group significantly in 4h and 24h(P<0.01). The infarct size of ischemic postconditioning group were lessen than cerebral ischemia group significantly at 4h and 24h(P<0.01).The observation of electronmicroscope displayed that the impairment of mitochondria and endoplasmic reticulum in neurons of hippocampal CAl area was reduced by ischemic postconditioning and pharmacologic postconditioning with histidine. The brain water content in Is+His group was increased than ischemic postconditioning group significantly at 4h(P<0.05). The brain water content in histidine group was increased than ischemic postconditioning group significantly at 24h(P<0.01). The rCBF had no significant change in Is+His group and ischemic postconditioning group at 4h(P>0.05). The rCBF in Is+His group were increased than ischemic postconditioning group significantly in 24h(P< 0.01).The infarct size had no significant changes in Is+His group and ischemic postconditioning group at 4h(P>0.05). The infarct size of Is+His group were increased than ischemic postconditioning group significantly in 24h(P<0.01).Conclusion:â‘ Ischemic postconditioning and pharmacologic postconditioning with histidine show the neuroprotective effect and they both could decrease infarct size, slow down brain water content, improve rCBF, and lighten the pathological structure changes of neuron in hippocampal CAl area.â‘¡schemic postcondionting is better than pharmacologic postconditioning with histidine in reducing local encephaledema and infarct size. Both of them have the same effect in improving hemodynamics in early ischemia, but pharmacologic postconditioning with histidine is better than ischemic postconditioning in improving regional cerebral blood flow.â‘¢Neuroprotective effect of ischemic postconditioning on thrombotic cerebral ischemic injury is more effective than pharmacologic postconditioning with histidine.