The Effect of Agmatine on Expression of MMP2 and MMP9 in Cerebral Ischemia

Kim, Jae Hwan; Lee, Yong Woo; Kim, Jae Young; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

Abstract

Agmatine is a primary amine formed by decarboxylation of L-arginine synthesized in the mammalian brain. Recent studies have shown that agmatine is neuroprotective in models of trauma and ischemia. The purpose of this study was to evaluate the effect of agmatine on the expression of MMP2 and MMP9, which are expressed in reperfusion injury following cerebral ischemia. Mice were subjected to 2 h middle cerebral artery occlusion and 22 h reperfusion. Agmatine (100 mg/kg) was administered intraperitoneally at the start of reperfusion. Agmatine treatment significantly reduced the immunoreactivity of MMP2 and MMP9 in the cortex, striatum, and penumbra on the ipsilateral side. The immunoreactivity of MMP2 and MMP9 was markedly lower in blood vessels of the agmatine-treated group than in the experimental control group. Immunoblot analysis showed that agmatine treatment decreased the expression of MMP2 and MMP9. After exogenous agmatine administration, the expression of agmatine was higher in the striatum and penumbra of the agmatine-treated group than in the experimental control group. The fluorescence intensity was markedly greater in blood vessels in the agmatine-treated group than in the experimental control group. These data suggest that agmatine might decrease the expression of MMP2 and MMP9 by regulating NOS activity, and thereby modulating NO synthesis.