Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia

Abstract Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke.