on August 19, 2004
Published online before print August 19, 2004, doi: 10.1161/01.STR.0000141160.66818.24
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 27, 2004
From the Institut de Neurociènces and Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Spain. * To whom correspondence should be addressed. 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.
Revised on May 6, 2004
Accepted on July 6, 2004
Histamine H2-Receptor Antagonist Ranitidine Protects Against Neural Death Induced by Oxygen-Glucose Deprivation
Cristina Malagelada PhD;
Key words: apoptosis • cerebral ischemia • neuronal death • stroke
This article has been cited by other articles:
 |
|
 |
|
  W. Hamabe, R. Fujita, and H. Ueda Insulin Receptor-Protein Kinase C-{gamma} Signaling Mediates Inhibition of Hypoxia-Induced Necrosis of Cortical Neurons J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1027 - 1034. [Abstract] [Full Text] [PDF]
|
|