Role of Endogenous Prostaglandins on Kainic Acid Induced Seizure Activity

It is not well clarified whether NSAID including COX-2 inhibitors aggravates the epileptic seizure. Pretreatments with NSAID(nonsteroidal anti-inflammatory drug) including COX-2 inhibitors such as indomethacin, nimesulide and celecoxib is known to aggravate the kainic acid(KA)-induced seizure activity. However it is not known whether the pro-conversant effect of NSAID was due to the change of endogenous prostaglandins(PGs) and if so, what types are involved. This study was done to determine the effect of prostaglandins administered intra-cisternally on the KA-induced seizure activity aggravated by pre-treated or post-treated with COX-2 inhibitors. Systemic KA injection (10 mg/ kg; i.p.) in mice evoked seizure sub-clinically within 15 min, and the seizure activity were measured with rating scales. PGs were administrated intracisternally 20 min prior to KA administration. COX inhibitors (indomethacin, nimesulide and ketoprofen) were injected 1h before or 15 min after KA. An additional COX-2 inhibitor, celecoxib, was administered intragastrically. Intracisternally administered PGF2α (700 ng), but not PGD2 (700 ng) and PGE2 (700 ng) completely alleviated KA-induced seizure activity potentiated by COX-2 inhibitors. PGF2α alone did not change the behavior on KA-induced seizure, however a FP receptor antagonist, AL 8810 (10 ng or 50 ng), an 11β-fluoro analog of PGF2α aggravated KA-induced seizure activity dose-dependently. Thus, pre-treated or post-treated COX-2 inhibitors aggravates KA-induced convulsions, and was involves changes in endogenous PGF2α. Seizure-induced through PGF2α might act as endogenous anticonvulsant through FP receptors.

Author dc:creator

• 김, 희재

Contributors dc:contributor

• 백, 은주
• 대학원 의학과
• 200524170

• seiszure
• NSAID
• COX
• prostaglandin
• Kainic acid

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000002224
000000002224

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1348