In Female Diabetic Rats, Cerebral Micro Vascular Matrix Metalloproteinase-3 (MMP3) Contributes to Vascular Injury Following a Stroke

Author(s): J Thomas*

After a stroke, diabetes makes Hemorrhagic Transformation (HT) worse and affects clinical outcomes. Diabetes in women increases the likelihood of stroke and has a negative impact on recovery. HT in male rats is mediated by activation of Matrix Metalloprotease 3 (MMP3) in hyperglycemic conditions, as we have demonstrated. The purpose of the current study was to test the hypotheses that, in light of our recent findings those diabetic female rats develop greater HT: 1) Cerebral microvascular MMP3 actuation adds to poor utilitarian results and expanded hemorrhagic changes (HT) after ischemic stroke, and 2) MMP3 restraint can work on practical results in female diabetic rodents. Middle Cerebral Artery Occlusion (MCAO) was performed for 60 minutes on diabetic and control wistar female rats. A single dose of an MMP3 inhibitor (UK356618 ) was administered to diabetic animals in one cohort. 15 mg/kg or automobile following reperfusion. Brain tissue was tested for neurobehavioral outcomes, brain infarct size, edema, HT, and MMPs. Day 3 after a stroke, diabetic rats had significant neurological impairments. Both the micro and macro vessels of diabetic animals showed significant increases in MMP3 expression and enzyme activity. Brain edema and HT scores were both reduced and functional outcomes were improved by MMP3 inhibition. All in all, cerebral endothelial MMP3 actuation to vascular injury in female diabetic rodents. MMP3 is identified as a potential therapeutic target for diabetic stroke by our findings.