ANIMAL MODEL OF EXCITOXICITY WITH NEUROINFLAMMATION Excitotoxicity is thought to contribute to brain damage in human diseases, including Alzheimer disease and bipolar disorder. We developed an animal model of excitotoxicity, the rat to which the glutamate receptor agonist, N-methyl-D-aspartate (NMDA), is administered daily for 21 days. The brain of this rat demonstrated upregulated markers of AA metabolism, and increased neuroinflammatory markers (interleukin-1beta, tumor necrosis factor alpha, glial fibrillary acidic protein and inducible nitric oxide synthase). This model might be used to develop drugs that suppress the upregulated arachidonic metabolism of excitotoxicity-neuroinflammation, and to further understand pathological mechanisms (Ref.3,1). ARACHIDONIC AND DOCOSAHEXAENOIC ACID METABOLITES IN ISCHEMIC BRAIN Biologically active metabolites of AA and docosahexaenoic acid (DHA) arise during brain ischemia and other brain insults, and can influence cell death and neuroprotection. We used reversed phase liquid chromatography/tandem mass spectrometry to quantify their production in rat brain subjected to cerebral ischemia and removed after head-focused microwave irradiation to stop postmortem metabolism. Brain AA, DHA and docosapentaenoic acid (n-6) concentrations were increased 18-, 5- and 4-fold compared to control values, respectively. Prostaglandin E2 and D2 were not detected in control brain. Concentrations of thromboxane B2, E2/D2-isoprostanes, 5-HETE, 5-oxo-ETE, and 12-HETE (other eicosanoids) were significantly elevated by ischemia, as was 17-hydroxy-DHA, the immediate precursor of neuroprotectin D1. These alterations in the balance of lipid mediators likely mediate brain injury and recovery (Ref.2).
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