Experimental Studies Of Expression Of TNF-α/MMP-9 After Focal Cerebral Ischemia/Reperfusion In Rats

Background and purpose: More attention is payed to how to reduce the disability and mortality after cerebral ischemia. The secondary brain injury -inflammation and edema formation contributes significantly to mobidity and mortality after cerebral ischemia. Matrix metallo-proteinase-9 (MMP-9) can degrade extracellular matrix, distroy vessel basemembrane and induce edema formation. Tumor necrosis factor- a (TNF- a ) may act as an operator in ischemic inflammation. It can also affect the edema formation. The reaction of association between MMP-9 and TNF- a is more emphasized by this study. The objection of this study is to observe the alteration of expression of MMP-9 / TNF- a in rats brain tissue after ischemic reperfusion, to explore both MMP-9 andTNF- a reaction on edema.By using of transmission electron microscope, try to identify the ultrastructure change of the lesion on ischemic reperfusion brain. Method: Rat model of ischemic reperfusion of cerebral middle artery was established. Rats were randomly divided into sham operation group and experimental groups. After 3h, 6h, 24h, 48h, 5d of reperfusion morphological studies were performed in serial sections. By using immunohistochemical SABC staining method and color image analysis, the expression of TNF- a and MMP-9 in cerebral cortex were measured after ischemic reperfusion. Brain edema was assayed by using dry-wet weight method. The infarct volume was measured by TTC staining and pathological changes were observed with transmission electron microscope.Results: Compared with other groups, the number of positive cells of TNF- a in 6 hour reperfusion group remarkly increased. (P<0.01) At the same time there is a marked decrease of grave value of TNF- a -postive cellbodies. The amount of MMP-9 postive cells was markedly increased after 24hour reperfusion. (P<0.01) Brain water content in the 24h and 48h groups were significantly increased, the same with the tendency of MMP-9. The infarction volume of 24h after reperfusion was much smaller than those of the consistent occlusion sample. Neuron edema and degeneration were clearly observed Endothelial cells edema was also displayed.Conclusions: The penumbra can be salvaged partly by MCAO2h and reperfusion. But reperfusion can also cause the brain injury. TNF- a is the key factor of the ischemic reperfusion. It can stimulate the neuron and the glial to combine and secrete MMP-9. MMP-9 can accelarate the angioedema if it was highly induced by ischemic reperfusion. The result showed that MMP-9 not only lead to angioedema formation but also play an important role in repair process.