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  • Title: An Na+/H+ exchanger inhibitor suppresses cellular swelling and neuronal death induced by glutamate in cultured cortical neurons.
    Author: Yamamoto S, Matsumoto Y, Suzuki Y, Tsuboi T, Terakawa S, Ohashi N, Umemura K.
    Journal: Acta Neurochir Suppl; 2003; 86():223-6. PubMed ID: 14753440.
    Abstract:
    We examined the effects of a selective Na+/H+ exchanger inhibitor, SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate), on neuronal death induced by glutamate in rat cortical neurons. Morphological changes in neurons were observed with a differential interference contrast microscope, and cellular swelling was analysed. Neuronal death was assessed by staining the cell with propidium iodide. The intracellular calcium concentration ([Ca2+]i) and the intracellular pH were measured by fluorescence imaging with fluo-3/AM as an indicator for [Ca2+]i and BCECF/AM for pH, respectively. SM-20220 (0.3 to 30 nM) dose-dependently attenuated glutamate (300 microM)-induced neuronal death in a dose-dependent fashion over 6 hours, and inhibited acute cellular swelling following glutamate (100 microM) exposure. SM-20220 suppressed the persistent [Ca2+]i increase following glutamate (500 microM) exposure, and inhibited intracellular acidification induced by glutamate (1 mM). The activation of the Na+/H+ exchanger system may enhance the progress of cerebral damage and oedema following glutamate exposure. SM-20220, a Na+/H+ exchanger inhibitor, suppressed neuronal death and cellular swelling induced by glutamate through inhibition of both Ca2+ influx and acidification in neurons.
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