Effect of dexamethasone, indomethacin, ibuprofen, and probenecid on carrageenan-induced brain inflammation

Journal of Neurosurgery
D A Gamache, E F Ellis

Abstract

A model of brain inflammation has recently been developed in mice using intraventricular injection of carrageenan (CAR). This model is characterized by increased brain water and vascular permeability, by neutrophil extravasation, and by evidence of increased pro-inflammatory arachidonic acid metabolites. The purpose of the current experiments was to determine the mechanism(s) by which CAR induces brain inflammation and to determine the utility of the CAR model in testing systemically administered therapeutic agents for their capacity to inhibit brain inflammation. Dexamethasone inhibited the increased brain water but not the increased vascular permeability produced by CAR. Indomethacin, an inhibitor of prostaglandin formation, suppressed peripheral inflammation produced by local injection of CAR but not brain inflammation produced by intraventricular CAR injection. Subsequent studies with carbon-14-labeled indomethacin showed that indomethacin penetrates peripheral tissues but is excluded from normal brain or brains inflamed by injection of CAR. Ibuprofen, another prostaglandin synthesis inhibitor, also had no effect on brain inflammation. Probenecid, an organic acid transport inhibitor, completely inhibited CAR-induced brain i...Continue Reading

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Citations

Mar 1, 1992·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·J E OlsonF A Jolesz
Feb 21, 2002·Journal of Neurotrauma·Sean D HurleyM Kerry O'Banion
Sep 12, 2009·European Journal of Pharmacology·Eniko VamosLaszlo Vecsei
Jun 1, 1988·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Y ShapiraE Shohami

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