Effect Of Resuscitation After Selective Cerebral Ultra-deep Hypothermia Blood Flow Occlusion On TGF-β₁ And MMP-9: An Experimental Study On Monkeys

[Objective]To observe the expression of TGF-β₁ and MMP-9 in monkeys of resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion.[Method] Nine 4-10-year-old rhesus mulattas were divided randomly into two groups: group A (bilateral internal carotid arterys would be occluded and 37℃Ringer's solution would be infused in operation) and group B (bilateral internal carotid arterys would be occluded and 4℃Ringer's solution would be infused in operation). Exposed bilateral external jugular veins (EJVs), bilateral external carotid arterys (ECAs), bilateral internal carotid arterys (ICAs) and bilateral internal jugular veins (IJVs). Right IJV intubated to monitoring central venous pressure (CVP). A catheter was inserted into right ICA to infuse cold Ringer's solution, two catheters were distally and proximally inserted into IJVs to extract the hypothermic diluted blood for ultrafiltration and then perfuse the warm blood into the right venae cava inferior after rewarming. Total body was heparinizated before reduce the brain temperature. Both ICAs were clamped 10 minutes. Then the both EJVs and the left IJV were clamped about 60 minutes. 4℃cold Ringer's solution was immediately perfused into the right ICA to induce the brain cooling less 16℃in group B, 37℃Ringer's solution was immediately perfused into the right ICA in group A. After 60 minutes, perfusion was stopped and blood vessels were recovered blood stream to cause brain physio-rewarming in group B, it didn't occur in group A of course. During preoperative and postoperative course,MRI scans were obtained and changes of hemodynamics were measured; the afunctional scales of neurology were done three days after operation. The monkeys' brain was immediately removed soon after death of group A in operation, and so did it in group B after we executed the monkeys 12 weeks after operation, followed by fixation,dehydration,embedding with paraffin and section. Immunohistochemical technique was used to determine frontal cellular expression of TGF-β₁ and MMP-9 in respective group. Statistics were analyzed by ANOVA analyses with significance level at P＜0．05． [Results] All monkeys of group A were not resuscitation after perfusion and died. The level of TGF-β₁ protein expression was low and the level of MMP-9 protein expression was overly high in group A. All monkeys of group B were succeeded in being built up the model. The hemodynamical parameters were steady during the operation, and all of them lived up till they were executed. MRI scan was normal after operation and the function of neurological deficient scale was normal. The level of TGF-β₁ protein expression was significantly higher in the group B than it in the group A (P<0．05) . The level of MMP-9 protein expression was significantly lower in the group B than it in the group A (P＜0．05) .[Conclusion] It is safety that monkeys resuscitate from selective cerebral ultra-deep hypothermia and blood flow occlusion of bilateral internal carotid for 60 minutes, and it is normal to the hemodynamical parameters and nervous function. The level of TGF-β₁ expression is significantly increased and the level of MMP-9 expression is significantly decreased after resuscitation after selective cerebral ultra-deep hypothermia and blood flow occlusion. It is an endogenous self-protective mechanism for helping to maintain neuron survival and to recover neural function. To most extent, mild cerebral ischemic lesion lead to neurocyte apoptosis and serious cerebral ischemic lesion lead to neurocyte necrosis.