Research article

Detrimental effects of tropisetron on permanent ischemic stroke in the rat

Eduardo Candelario-Jalil^1,2 , Eduardo Muñoz³ and Bernd L Fiebich^1,4

¹Neurochemistry Research Group, Department of Psychiatry, University of Freiburg Medical School, Hauptstr. 5, D-79104 Freiburg, Germany

²Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA

³Departamento de Biología Celular, Fisiología e Inmunología. Universidad de Córdoba, Avenida Menéndez Pidal s/n. 14004, Córdoba, Spain

⁴VivaCell Biotechnology GmbH, Ferdinand-Porsche-Str. 5, D-79211 Denzlingen, Germany

author email corresponding author email

BMC Neuroscience 2008, 9:19doi:10.1186/1471-2202-9-19

Published:	6 February 2008

Abstract

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.