Expression of COX-2 by normal and reactive astrocytes in the adult rat central nervous system

We have used a previously characterized antiserum against cycloxygenase-2 ( COX-2) together with cold methanol fixation to immunohistochemically locate the protein in astrocytes in rat brain. Although in cerebral cortex most e nzyme was located in neuronal perikarya as previously described, a number o f glial fibrillary acidic protein (GFAP)-positive astrocytes were also labe led. No COX-P-positive neurons were seen in the cerebellum, but here also a subset of GFAP+ astrocytes was present which contained the enzyme. The num ber of COX-P-positive astrocytes increased considerably after injection of the neurotoxin kainate into the cerebellum. These immunohistochemical data were supported by semiquantitative RT-PCR results, which were used to asses s the levels of COX-2 mRNA relative to the housekeeping gene hypoxanthine p hosphoribosyl transferase. PGE(2) levels were measured in contralateral and lesioned cerebellum to correlate changes in COX-2 immunoreactivity and mRN A with physiological events. PGE(2) levels increased by 230% in the lesione d cerebellar hemispheres in comparison to the contralateral ones, We discus s the possibility that the targets for astrocytic prostaglandins might incl ude both autocrine effects and paracrine responses of neurons, lymphocytes and capillary endothelial cells.