Abstract
Cyclooxygenases (COX) are potent mediators of inflammation, blood flow and immunomodulation in the pathologically altered brain. Two COX iso-enzymes have been associated with brain disease, the constitutively expressed COX-1 and the cytokine-inducible COX-2. Here we have analyzed the localization of COX-1 and COX-2 in the mouse kindling model by immunohistochemistry. Bipolar electrodes were implanted in the left side of the mouse amygdala. Mice were stimulated once a day with a biphasic 60 Hz square wave pulse at 80-150 μA. Seizure development was evaluated with Racine's criterion. Mice brains were perfused and fixed at C0 (sham), C3 and C5 stages, respectively. Brains were sectioned and immunostained with several antibodies. COX-1 was predominantly observed in microglia and increased in the hippocampus and areas around third ventricle as seizure development. On the other hand, COX-2 predominantly observed in neurons and increased in the hippocampus. These regions are proposed to play important role in the propagation of limbic seizures. Moreover, both SC-560 (an inhibitor to COX-1) and nimesulide (an inhibitor to COX-2) suppressed the progression of kindling stage, however, did not decrease kindling stage after completion of epileptogenesis. While precise mechanism of COX positive cells such as microglia is not clear, results suggest the involvement of both COX-1 and COX-2 in epileptogenesis and inhibitors to COX might be useful to prevent seizure development. [J Physiol Sci. 2006;56 Suppl:S241]
