Detrimental effects of tropisetron on permanent ischemic stroke in the rat.

Neurochemistry Research Group, Department of Psychiatry, University of Freiburg Medical School, Hauptstr, 5, D-79104 Freiburg, Germany. ecandelario-jalil@salud.unm.edu

BACKGROUND: Recent in vitro evidence indicates that blockade of 5-hydroxytryptamine (5-HT) receptor 3 (5-HT3) is able to confer protection in different models of neuronal injury. The purpose of the present study was to investigate the effect of tropisetron, a 5-HT3 receptor antagonist, on infarct size and neurological score in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in the rat. METHODS: Two different doses of tropisetron (5 and 10 mg/kg) or vehicle were administered intraperitoneally 30 min before pMCAO. Neurological deficit scores, mortality rate and infarct volume were determined 24 h after permanent focal cerebral ischemia. RESULTS: Tropisetron failed to reduce cerebral infarction. Animals receiving tropisetron showed a significant increase (p < 0.05) in neurological deficits and mortality rate. CONCLUSION: Data from this study indicate that blockade of 5-HT3 receptors with tropisetron worsens ischemic brain injury induced by pMCAO. These findings could have important clinical implications. Patients taking tropisetron, and possibly other 5-HT3 antagonists, could potentially have a worse outcome following a brain infarct.

PMID: 18254974 [PubMed - indexed for MEDLINE]

PMCID: PMC2259310