Title: A Non-Steroidal Anti-Inflammatory Agent Provides Significant Protection During Focal Ischemic Stroke with Decreased Expression of Matrix Metalloproteinases
Volume: 4
Issue: 3
Author(s): Yan Wang, Xiu-Ling Deng, Xiang-Hua Xiao and Bing-Xiang Yuan
Affiliation:
Keywords:
Nimesulide, neuroprotection, embolic focal cerebral ischemia, thrombolytic reperfusion, matrix metalloproteinases, hemorrhage transformation
Abstract: The present study was designed to investigate whether the neuroprotective effect of nimesulide was mediated by inhibiting expression of matrix metalloproteinase-9 (MMP-9) and/or matrix metalloproteinase-2 (MMP-2) in a rat model of thrombolytic reperfusion after the embolic focal cerebral ischemia (FCI). It was found that nimesulide at therapeutically relevant doses (3, 6 and 12 mg/kg) decreased neurological deficits, infarct volume, brain index and brain water content in a dose-dependent manner. Hemorrhagic transformation was reduced by 64% with treatment of 12 mg/kg nimesulide. Quantitative analysis of immunohistochemical staining of brain slices showed that the neuron number expressing MMP-9 and MMP-2 increased in the model animals treated with vehicle (p < 0.01 vs sham group), and significantly decreased in nimesulide-treated animals (p < 0.05 or p < 0.01 vs vehicle group). Our results demonstrate that nimesulide significantly reduces the degree of neuronal injury and hemorrhage transformation caused by thrombolytic reperfusion after the embolic FCI, and that inhibition of MMP-9 and MMP-2 expression contributes at least in part to the neuroprotection.
