The Relationship Between Matrix Metalloproteinase-9 Expression And Cerebral Water Content In Rats After Intracerebral Hemorrhage

Matrix metalloproteinases are a gene family of zinc - containing extracellular - matrix ( ECM) degrading proteolytic enzymes. They are important in normal development, wound healing, and angiogenesis and have been implicated in numerous pathological processes, including atheriosclerosis, arthritis, tumor growth and metastasis, and MS. The endogenous tissue inhibitors to metalloproteinases ( TIMPs) can inhibit their activities. Both MMPs and TIMPs modulate capillary permeability. The balance between them was broken down and the pro-teolysis enhanced which was related to the meuroinflammatory reponse. Studies recently show that MMP - 9 of the family connected closely with the brain edema following ICH by over - degrading the ECM. The ECM is a multifunctional complex of proteins and proteoglycans assembled in a highly organized manner that contributes to the structural integrity of cells and tissue within an organ system. The basement membrane, which provides structural support to the vasculature, is composed of ECM molecules such as type IV collagen, laminin, and fibronec-tin. In brain, the endothelial cell wall, strengthened by tight junctions, defines the blood - brain barrier (BBB). The extracellular matrix molecules constitute the basement membrane underlying the vasculature and play a critical role in maintaining the integrity of the BBB. After stroke, there is a breakdown of the BBB by activated MMP -9 with an associated increase in vascular permeability, inflammatory cell influx, and neuronal cell death. The present study was designed to investigate the expression of MMP -9 and the changes of cerebral water content in rats following intracerebral hemorrhage (ICH).MethodsICH model was produced by stereotactically infusing 75 ul autologous fresh blood taken from rat femoral artery into the right caudate nucleus. MMP -9 protein expression was detected by zymogram analysis over a time course ranging from 6 hours to 10 days, Immunohistochemistry at 24 hours was utilized to characterize the expression of MMP - 9 after stroke. The cerebral water content was measured by dry - wet weight method.ResultsThe expression of MMP - 9 and cerebral water content in the hemorrhage site increased progressively over time after ICH. After 6 hours, significant (p <0.05) cerebral water content and MMP - 9 activity were observed and reached maximum levels by 24 hours ( p < 0. 01) , then persisted for 3 days at this level . Brain water content returned to basal levels by 6 days while MMP - 9 expression still maintained a lower level by 6 days. And immunohistochemical analysis of MMP - 9 expression induced in rat brain 24h after ICH. MMP - 9 expression was not observed in contralateral brain and control group but was identified within and at the periphery of the lesion cortical region.ConclusionsThese results demonstrate that early increased MMP - 9 expression and cerebral water content were significant responses to ICH; MMP - 9 contributes to the brain edema.