Research

Effects of the cyclooxygenase-2 inhibitor nimesulide on cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion in the rat

Eduardo Candelario-Jalil^1,2 , Noël H Mhadu¹ , Armando González-Falcón¹ , Michel García-Cabrera¹ , Eduardo Muñoz³ , Olga Sonia León¹ and Bernd L Fiebich^2,4

¹  Department of Pharmacology, University of Havana (CIEB-IFAL), Havana 10600, Cuba

²  Neurochemistry Research Group, Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, D-79104 Freiburg, Germany

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

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

author email corresponding author email

Journal of Neuroinflammation 2005, 2:3doi:10.1186/1742-2094-2-3

Published:	18 January 2005

Abstract

Background

Previous studies suggest that the cyclooxygenase-2 (COX-2) inhibitor nimesulide has a remarkable protective effect against different types of brain injury including ischemia. Since there are no reports on the effects of nimesulide on permanent ischemic stroke and because most cases of human stroke are caused by permanent occlusion of cerebral arteries, the present study was conducted to assess the neuroprotective efficacy of nimesulide on the cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion (pMCAO) in the rat.

Methods

Ischemia was induced by permanent occlusion of the middle cerebral artery in rats, via surgical insertion of a nylon filament into the internal carotid artery. Infarct volumes (cortical, subcortical and total) and functional recovery, assessed by neurological score evaluation and rotarod performance test, were performed 24 h after pMCAO. In initial experiments, different doses of nimesulide (3, 6 and 12 mg/kg; i.p) or vehicle were administered 30 min before pMCAO and again at 6, 12 and 18 h after stroke. In later experiments we investigated the therapeutic time window of protection of nimesulide by delaying its first administration 0.5–4 h after the ischemic insult.

Results

Repeated treatments with nimesulide dose-dependently reduced cortical, subcortical and total infarct volumes as well as the neurological deficits and motor impairment resulting from permanent ischemic stroke, but only the administration of the highest dose (12 mg/kg) was able to significantly (P < 0.01) diminish infarct volume. The lower doses failed to significantly reduce infarction but showed a beneficial effect on neurological function. Nimesulide (12 mg/kg) not only reduced infarct volume but also enhanced functional recovery when the first treatment was given up to 2 h after stroke.

Conclusions

These data show that nimesulide protects against permanent focal cerebral ischemia, even with a 2 h post-treatment delay. These findings have important implications for the therapeutic potential of using COX-2 inhibitors in the treatment of stroke.