プロスタグランジンE合成酵素-1の誘導はマウス脳出血モデルにおける神経炎症と神経学的運動障害に寄与する

抄録

We have demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE₂ synthesis, is a critical factor of stroke-reperfusion injury. In this study, we investigated the role of mPGES-1 in neuroinflammation and neurological dysfunctions observed after intracerebral hemorrhage (ICH). Collagenase was injected into the left striatum of adult mPGES-1 knockout (KO) and wild-type (WT) mice. In WT mice, mRNA and protein of mPGES-1 were significantly up-regulated in striatum and cerebral cortex after ICH. In mPGES-1 KO mice, although the hemorrhage and edema size were almost the same as WT mice, survival rate was significantly higher than WT mice. The PGE₂ production, TNF-α induction and glial activation after ICH in mPGES-1 KO brain were significantly less than those in WT brain. DAPI and TUNEL staining showed ICH-induced nuclear condensation and DNA fragmentation in mPGES-1 KO striatum were less than those in WT striatum. Furthermore, mPGES-1 KO mice showed better performance in stepping error test, rotarod test and neurological dysfunction scoring compared with the WT mice. These results suggest that mPGES-1 contributes to ICH-induced neuroinflammation, neuronal apoptosis, neurological dysfunctions and mortality through PGE₂ production. Thus, mPGES-1 may be a new therapeutic target for ICH.