Histamine H2-receptor antagonist ranitidine protects against neural death induced by oxygen-glucose deprivation.
OBJECTIVE
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.
Institut de Neurociènces and Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Spain.
Cristina
C
Malagelada
Xavier
X
Xifró
Nahuai
N
Badiola
Josefa
J
Sabrià
José
J
Rodríguez-Alvarez
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D009336:Necrosis; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats
D006635:Histamine H2 Antagonists; D018696:Neuroprotective Agents; D011899:Ranitidine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose; D010100:Oxygen