Over-express endothelin-1 in astrocyte lead to increased brain damage and altered cytokine expression after cerebrl ischemia

Abstract

Previously, we reported that the expression of endothelin (ET-1) is induced in astrocytes and endothelial cells after cerebral hypoxia/ischemia. Recently, we also showed that transgenic mice over-expressing ET-1 in astrocytes displayed more severe neurologic deficits and increased brain infract following transient middle cerebral artery occlusion (MCAO for 2 h followed by 22 h reperfusion) compared with those of non-transgenic mice. However, the underling mechanism for further brain damage in these transgenic mice with astrocytic ET-1 over-expression is not yet clear. ET-1 has been shown to stimulate leukotriene (LTB4) and cytokine expression such as interleukin 6 (IL-6) after MCAO, which may contribute to brain inflammation and damage. Here, we investigated cytokine expression in brain of astrocytic ET-1 transgenic mice to determine whether the altered cytokine expressions may have lead to further brain damage in these transgenic mice. Group of transgenic and non-transgenic mice were exposed to either sham or transient MCAO. Cytokine mRNAs from these mouse brains were detected by using the RiboQuant multi-Probe Ribonuclease Protection Assay system. The brain of astrocytic ET-1 transgenic mice treated with the transient MCAO showed increased level of macrophage migration inhibitory factor (MIF), whereas IL-6 level did not show any changes. The present data suggest that altered expression of MIF in the brain of astrocytic ET-1 transgenic mice may have contributed to more severe neurologic deficits and increased brain damage after MCAO.