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Neuroprotection of cultured cortical neurons mediated by the cyclooxygenase-2 inhibitor APHS can be reversed by a prostanoid by Noel G. Carlson is a Neuroscience article available to read on EtoBox.

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The neuroprotective properties of two cyclooxygenase-2 (COX-2) specific inhibitors, N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS398) and o-(acetoxy-phenyl)hept-2-ynyl2 sulfide (APHS) were examined in vitro using a mixed cortical neuronal culture system. Each of these inhibitors conferred a concentration-dependent neuroprotective effect against an excitotoxic assault induced by NMDA. Neuroprotection was observed when the COX-2 inhibitor was added before or even 1-3 hours after NMDA, which was coincident with an NMDA-induced increase of COX-2 transcripts in neurons. To test whether these COX-2 inhibitors confer neuroprotection by inhibiting biosynthesis of prostanoids that may contribute toward excitotoxicity, two NMDA-induced prostanoids, PGE(2) and PGF(2alpha), were tested for their ability to reverse the neuroprotective properties of APHS. APHS-mediated neuroprotection was overcome by the concentration-dependent (as low as 100 nM) administration of a synthetic analog of PGE2, 17-phenyl-trinor-PGE(2) (17-pt-E(2)), which is a relatively specific agonist for the EP1 and EP3 prostaglandin receptors; however, PGF(2alpha) had no significant effect on neuroprotection confer

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Author

Noel G. Carlson

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0360-4012)

Published

2002

Language

EN

Field

Neuroscience (Life Sciences)