A Study Of The Role For Matrix Metalloproteinases And Tissue Inhibitor Of Mettalloproteinasese After Cerebral Ischemia Reperfusion Injure In Rat

Background and purpose: Cerebral ischemic reperfusion injury (IRI) is a dangerous complication that most frequently met in the clinic. It is usually accompanied by many diseases, such as brain trauma brain tumor and cerebralvasocular diseases. It's a common response of brain to the injury and has the decisive role to the prespection of primitive disease. With the IRA exacerbating, the intracranial pressure increases, usually induces vasogenic brain edema (VBE) and tonsillar hernia. The death rate is high but there is no effective method to control. Some study had suggested that permeability of blood-brain barrier (BBB) changed when VBE formed. The utrastructure of BBB consists of endothelial cells of capillary vesse1~ basal lamina and glioma cells. This structural integrity of BBB is important in keeping normal physiological function. Matrix metalloproteinases (MMPs) are a gene family of enzymes that degrade extracellular matrix (ECM) molecules. However, ECM is important in maintaining a neuronal microenvironment. Gelatinase B (MMP-9) ,a member of the MMP family, attacks basal lamina macromolecules, including the type IV collagen around cerebral capillaries.TIMP-1 is the specific endogenous inhibitor of MMP-9.They keep the balance of interaction in physiological state. When cerebral ischemic reperfusion injury occurred, the balance between MMP-9 and TIMP-l was disturbed, favoring a shift to proteolysis. The result was increasing the blood- brain barrier permeability and forming vasogenic brain edema. BB-94, a synthetic matrix metalloproteinase inhibitor, can reduce this damage. Therefor, MMP and TIMP play important role to BBB damage in cerebral ischemic reperfusion injury. Metalloproteinase inhibitors may provide a new therapeutic approach to prevent proteolysis, preserve the extracecellular matrix and promote recovery from brain injury. Mater i a I s and Methods: The male adult Wistar rats were employed and divided into 4 groups randomly: normal group, sham-operated group, ischemic group, enzyme inhibitor group. Animal model was made by method of Pulsinelli. BBB permeability reflected by Even's blue extravasation, Water content of brain tissue was observed and confirmed by direct wet/dry tissue measurements. Histological sections were stained by HE and checked by optical microscopy. Utrastructure of BBB was checked by electron microscopy. The respective proteins of MMP-9 and TIMP-1 were identified by immunocytochemistry. Resu Its: EB extravasation: there was no significantly difference between normal group and sham-operated group; it increased at 3, 48 hours in ischemic group. Only after3 and 48 hours of reperfusion, enzyme inhibitor group was apparently lower than ischemic group. It showed that cerebral ischemic reperfusion injury improved BBB permeability, BB-94 could decrease BBB permeability significantly. The water content: there was no significantly difference between normal group and sham-operated group; it increased gradually after 3 hours of reperfusion and was maximal at 48 hours in ischemic group. It was significantly lower in enzyme inhibitor group at 24, 48 hours. The statistic analysis indicated that BB-94 could decrease water content significantly. HE histological sections: The density of neurocyte in hippocampi CAl area was 240?14.0(number of neurocyte/mm) in normal group, there was no significantly difference to sham-operated group. After 3,7 days of reperfusion ,the density in ischemic group was 10.5 ?.0,...