Stage- and region-specific cyclooxygenase expression and effects of a selective COX-1 inhibitor in the mouse amygdala kindling model.
In an attempt to elucidate the involvement of cyclooxygenase (COX) enzymes, particularly COX-1, in epileptogenesis, the localization of COX-1 and COX-2 expression in the mouse kindling model was analyzed by immunohistochemistry. COX-2 was predominantly observed in brain neurons and its concentration in the hippocampus increased with progressing seizures, as reported previously. COX-1 was predominant in microglia and its concentration was also enhanced in the hippocampus and areas around the third ventricle during the progression of seizures. These regions are thought to play an important role in the propagation of limbic seizures. Moreover, the administration of SC-560 (a selective COX-1 inhibitor) or indomethacin (a non-selective COX inhibitor) retarded the progress of seizures. Although the precise function of COX-positive cells in microglia and elsewhere is not clear, our results suggest that COX-1 as well as COX-2 may be involved in epileptogenesis, and that certain COX inhibitors can potentially prevent the occurrence of seizures.
Tanaka
Shinji
S
Teikoku Seiyaku Co. Ltd., 567 Sanbonmatsu, Higashikagawa, Kagawa 769-2695, Japan.
Nakamura
Takehiro
T
Sumitani
Kazunori
K
Takahashi
Fumio
F
Konishi
Ryoji
R
Itano
Toshifumi
T
Miyamoto
Osamu
O
D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000201:enzymology; D007031:Hypothalamus / Q000201:enzymology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009044:Motor Cortex / Q000201:enzymology; D009474:Neurons / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; C115461:SC 560; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin