After focal cerebral ischemia, tumor necrosis factor-alpha deteriorates cerebral edema and survival rate. Therefore, tumor necrosis factor-alpha neutralization could reduce cerebral microvascular permeability in acute cerebral ischemia. Left middle cerebral artery occlusion for 120 mins followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Antirat tumor necrosis factor-alpha neutralizing monoclonal antibody with a rat IgG Fc portion (15 mg/kg) was infused intravenously right after reperfusion. Stroke index score, infarct volume, cerebral specific gravity, and the endogenous expression of tumor necrosis factor-alpha, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in the brain tissue were quantified in the ischemic and matched contralateral nonischemic hemisphere. In the antitumor necrosis factor-alpha neutralizing antibody-treated rats, infarct volume was significantly reduced (P=0.014, n=7; respectively), and cerebral specific gravity was dramatically increased in the cortex and caudate putamen (P<0.001, n=7; respectively) in association with a reduction in MMP-9 and membrane type 1-MMP upregulation. Tumor necrosis factor-alpha in the brain tissue was significantly elevated in the ischemic hemisphere 6 h after reperfusion in the nonspecific IgG-treated rats (P=0.021, n=7) and was decreased in the antitumor necrosis factor-alpha neutralizing antibody-treated rats (P=0.001, n=7). Postreperfusion treatment with antirat tumor necrosis factor-alpha neutralizing antibody reduced brain infarct volume and cerebral edema, which is likely mediated by a reduction in MMP upregulation.

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This study indicates that while there is a significant association between DD and measures of microvascular function, the relationship between endothelial dysfunction, CTGF and subtle measures of DD is not strong. Other factors are therefore likely to play an important role in the early pathogenesis of subclinical cardiac DD in type 2 diabetes.

Diabetes mellitus is characterized by a lack of insulin causing elevated blood glucose, often with associated insulin resistance. Over time, especially in genetically susceptible individuals, such chronic hyperglycemia can cause tissue injury. One pathological response to tissue injury is the development of fi brosis, which involves predominant extracellular matrix (ECM) accumulation. The main factors that regulate ECM in diabetes are thought to be pro-sclerotic cytokines and protease/anti-protease systems. This review will examine the key markers and regulators of tissue fi brosis in diabetes and whether their levels in biological fl uids may have clinical utility.