| Background and Objective : Epidemiological investigation indicated that acute cerebrovascular disease is the third disease cutthroat except cardiovascular disease and cancer, threatening health of mankind seriously, especially intracerebral hemorrhage(ICH) which with high mortality and maimed rate, coming on suddenly and riskily, was the biggest bane to human. Brain swelling often occurs around 1 to 2 days after an intracerebral hemorrhage, leading to clinical worsening. Cytotoxic and vasogenic brain edema occurs in the tissue around the mass and spreads to distant regions. The mechanisms of forming brain edema have not previously been explained. Matrix metalloproteinases (MMPs) are a family of zinc-binding proteolytic enzymes that are capable of degrading components of the extracellular matrix in a variety of physiological and pathophysiological conditions. Tissue inhibitors to MMPs are produced along with the enzymes. Excessive proteolysis activity due to an imbalance between MMPs and inhibitors leads to extracellular matrix disruption. Among MMPs, gelatinase A (MMP-2) and gelatinase B (MMP-9) are able to digest the endothelial basal lamina, which plays a major role in maintaining blood-brain barrier (BBB) impermeability, by regulating tight junctions leading to the opening of the BBB. In the pathological condition of ischemia / reperfusion, digestion of the endothelial basal lamina is reported to occur as early as 2 hours after ischemia, which may result in BBB permeability a few hours after ischemia. In a bacterial collagenase-induced ICH, MMPs and plasminogen activators are increased after 16 to 24 hours, when the brainedema is maximal in regions away from the hemorrhage site.This evidence suggested that proteolysis enzymes, which are induced in an area of hemorrhagic injury , might alter capillary permeability , leading to vasogenic brain edema . The cellular sources and time course of MMP-2 / MMP-9 expression and its contribution to ICH have not previously been studied. The present series of experiments were performed to define the time course of increased MMP-2 ,MMP-9, and TIMP-1 expression that occurs after ICH in the rat. In addition, Sodium aescinate was administered systemically to rats receiving ICH to determine whether it could reduce increased MMP-2 /MMP-9 expression after ICH and also explore the molecular mechanisms of the treatment of sodium aescinate used on ICH. Methods:1. The ICH animal models were established by stereotaxical injecting 0.4IU VII collagenase into the right globes pallidus(GP).2. Health SD rats were divided randomly for: normal contra! group(NG), sham-operated group (SG), intracerebral hemorrhage model group(MG), sodium aescinate treatment group A(TGA) in which sodium aescinate (Smg.kg-1.day-1 ) was abdomen injected daily and sodium aescinate treatment group B(TGB) in which sodium aescinate was 10mg.kg-1.day-1. Rats were sacrificed at 6, 24, 48, and 96 hours respectively after operation at the rate of 4 to 5 animals at each time point.3. The expression of MMP-2,MMP-9, and TIMP-1 gene mRNA in the ICH rat brains has been investigated by in situ hybridization.4. The expression of MMP-2,MMP-9, TNF-α, VEGF,and TIMP-1 protein in the ICH rat brains has been detected by immunohistochemistry.5. The BBB opening was evaluated by the Evans Blue extravasation method.6. Brain water content(BWC) was determined by comparison of wet and dry weight.Results:1. There are no encephaledema in the NG and SG group. Serious encephaledema happened in 6 hours after the rat cerebral hemorrhage, specially in the operation side. The peak was found at 24 hours and lasted 48 hous. After 96 hours, the descendence was obvious with the palpable enhancement in the operation side than SG. The moisture content of each encephalon area decreased clearly after the treatment of sodium aescinate with the negative dose-effect relationship.2. We found few EB in the brain of NG and SG. And the exosmose dose of EB of perihematom ( right...
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