Stromelysin‐1(MMP3) Worsens the Neurovascular Injury in Hyperglycemic Stroke.

Abstract

IntroductionAcute hyperglycemia (HG) worsens stroke outcomes and increases the risk of cerebral hemorrhage especially with the co‐administration of tissue plasminogen activator (tPA). Matrix metalloproteinase 3 (MMP3) mediates tPA‐induced hemorrhagic transformation (HT) after stroke. However, the role of MMP3 in hyperglycemic stroke is unknown. The goals of the study were to evaluate the impact of the severity of HG 1) on stroke outcomes and 2) on MMP3 activity and expression.MethodsMild and severe HG were induced by glucose injections in rats that were subjected to 90 min middle cerebral artery occlusion and 22.5 h reperfusion. Stroke outcome and cerebrovascular MMP3 activity were assessed. Brain microvascular endothelial cells (BVEC) are subjected to oxygen glucose deprivation (OGD) followed by HG and MMP3 expression was measured.ResultsSevere HG significantly increased the infarct size. Mild elevation in blood glucose has significantly increased HT and MMP3 activity in cerebral vasculature. HG increased MMP3 expression in BVEC and hypoxia potentiated this effect.ConclusionMild elevation in blood glucose worsens the vascular injury without increasing the infarct size. Up‐regulation of MMP3 in the cerebrovasculature and endothelial cells suggests that MMP3 highly contributes to the HG induced vascular injury.