脳におけるシクロオキシゲナーゼ: その局在と病態生理

抄録

Prostaglandins play various roles in the brain under physiological as well as pathological conditions. This review summarizes our present knowledge about brain localization of two isoforms of cyclooxygenase, enzymes responsible for prostaglandin biosynthesis, and their possible functions. Cyclooxygenase-1 (COX-1) is con-stitutively expressed in microglia throughout the brain. Little is known about COX-1 function there. COX-1 is also abundantly expressed in the primary sensory neurons both at their cell bodies and at the central terminals in the medulla and spinal cord suggesting its involvement in sensory signal transmissions. COX-2 is constitutively expressed in telencephalic neurons in an activity-dependent manner. This neuronal expression of COX-2 was reported to be involved in the regulation of regional cerebral blood flow. On the other hand, some studies have reported that COX-2 might exert adverse actions after brain ischemia and in Alzheimer's disease. Under various infectious as well as inflammatory conditions, COX-2 is expressed in brain endothelial cells. We presented a large body of evidence that elevation of prostaglandin EZ in the brain and occurrence of fever during infection/inflammation are the consequences of this endothelial expression of COX-2. Thus, brain endothelial cells seem to transmit blood borne cytokine signals to brain by producing prostaglandin E₂.