Neuroprotection of PGE2, but not 15d-PGJ2, on kainic acid-induced neurotoxicity on rat brain

• Main Authors: Nien-Chu Yu, 于念主
• Other Authors: Henrich Cheng
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/80455579427790300621

碩士 === 國立東華大學 === 生物技術研究所 === 92 === Prostaglandin E2 (PGE2), a product of arachidonic acid cyclooxygenase (COX) metabolism, has been known as an important inflammatory mediator. By contrast, 15d-PGJ2, a non-enzymatic metabolites of prostaglandin D2 (PGD2) and a specific PPAR-g agonist, is known to repress several inflammatory responses. Both PGD2 and PGE2 are abundant PGs in the brain. Despite the classic role of PGE2 as a proinflammatory molecule, much in vivo and in vitro evidence have demonstrated that exogenous PGE2 may protect glutamate toxicity in neurons. The present work examines whether exogenous PGE2 or 15d-PGJ2 is able to protect kainate-induced cell damage in the rat hippocampus. Infusion of kainate to rat hippocampal CA3 significantly induced neuronal damage as evidenced by (1) presence of Fluoro-Jade B positive cells (2) increment of IL-1b positive cells and COX-2 expression (3) increment of activated microglia (ED1 positive) number (4) reduction of neuronal number. Co-infusion of PGE2 with kainate (0.2mg / ml / CA3 region) to hippocampal CA3 alleviates kainate-induced neuronal loss and microglial activation. Furthermore, kainate-induced COX-2 expression was reduced by PGE2, while heme oxygenase-1 (antioxidative stress protein) expression was increased by PGE2. By contrast, co-infusion of 15d-PGJ2 with kainate did not have protective effect on kainate-induced toxicity. Taken together, PGE2, but not 15d-PGJ2, effectively protect hippocampal CA3 cells from kainate-induced damage.