Abstract 11673: Neuroprotective Mechanisms of Mefenamic Acid in an in vitro Model of Stroke

• Published in: Circulation (New York, N.Y.) N.Y.), 2016-11, Vol.134 (Suppl_1 Suppl 1), p.A11673-A11673
• Main Authors: Khansari, Parto S, Shaligram, Sonali S, Rahimian, Roshanak, Halliwell, Robert F
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.134.suppl_1.11673

IntroductionFenamates are classical non-steroidal anti-inflammatory drugs but they are also modulators of GABAA receptors, activators of potassium channels and antagonists of non-selective cation channels. Previous data from our lab has demonstrated that the fenamate, mefenamic acid (MFA), has neuroprotective effects both in vitro and in vivo.HypothesisWe hypothesized that the neuroprotective actions of mefenamic acid result from its diverse pharmacological properties. To test this hypothesis, we have investigated four pharmacological properties of MFA, namely cyclooxygenase (COX) inhibition, GABAA receptor modulation, potassium channel activation and reactive oxygen species (ROS) inhibition against glutamate neurotoxicity in vitro.MethodsNeurotoxicity was induced by exposure of embryonic rodent hippocampal neurons, 9 days in vitro, to 10 mins of Na-glutamate (5μM). 24 hours after exposure to Na-glutamate, cell death was quantified by measuring the levels of lactate dehydrogenase (LDH) in the media using a CytoTox-96 non-radioactive assay kit. Generation of ROS was measured using Carboxy-H2DCFDA dye.ResultsMFA and the non-fenamate COX inhibitors, ibuprofen, indomethacin and Na-salicylate were examined against glutamate neurotoxicity at 10 or 100μM. Cell death was significantly (p