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(Stroke. 2004;35:2396.)
© 2004 American Heart Association, Inc.

Original Contributions

Histamine H₂-Receptor Antagonist Ranitidine Protects Against Neural Death Induced by Oxygen-Glucose Deprivation

From the Institut de Neurociènces and Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Spain.

Correspondence to Dr Josefa Sabrià, Institut de Neurociènces, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, E-08193 Cerdanyola del Vallès, Bellaterra (Barcelona), Spain. E-mail Josefa.Sabria{at}uab.es

Background and Purpose— Administration of histamine receptor antagonists has been reported to produce contradictory results, either reducing or increasing neural damage induced by ischemia. In this study, we investigated the neuroprotective effects of histamine H₂-receptor antagonists in an "in vitro" model of ischemia.

Methods— Cultured rat brain cortical neurons were exposed to oxygen-glucose deprivation (OGD) in the presence or absence of different histaminergic drugs. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay. Necrosis and apoptosis were quantified by staining cells with propidium iodide and Hoechst 33258. Caspase 3 activation was determined by immunocytochemistry and Western blot.

Results— Pretreatment with H₂ antagonists effectively reduced neuronal cell death induced by OGD. Ranitidine decreased the number of necrotic and apoptotic cells. Caspase 3 activation and alteration of the neuronal cytoskeleton were also prevented by ranitidine pretreatment. The neuroprotective effect of ranitidine was still evident when added 6 hours after OGD.

Conclusions— H₂-receptor antagonists protected against OGD-induced neuronal death. Ranitidine attenuated cell death even when administered after OGD. These data suggest that this drug, which is currently used for the treatment of gastric ulcers, may be useful in promoting recovery after ischemia.

Key Words: apoptosis • cerebral ischemia • neuronal death • stroke

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