ROSIGLITAZONE, A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ LIGAND, REDUCES INFARCTION VOLUME AND NEUROLOGICAL DEFICITS IN AN EMBOLIC MODEL OF STROKE
Article first published online: 16 OCT 2006
Clinical and Experimental Pharmacology and Physiology
Volume 33, Issue 11, pages 1052–1058, November 2006
How to Cite
Allahtavakoli, M., Shabanzadeh, A. P., Sadr, S. S., Parviz, M. and Djahanguiri, B. (2006), ROSIGLITAZONE, A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ LIGAND, REDUCES INFARCTION VOLUME AND NEUROLOGICAL DEFICITS IN AN EMBOLIC MODEL OF STROKE. Clinical and Experimental Pharmacology and Physiology, 33: 1052–1058. doi: 10.1111/j.1440-1681.2006.04486.x
- Issue published online: 16 OCT 2006
- Article first published online: 16 OCT 2006
- Received 22 November 2005; revision 29 March 2006; accepted 3 April 2006.
- 1Stroke is accompanied by a robust inflammatory response, glutamate-mediated excitotoxicity, release of reactive oxygen species and apoptosis. Thiazolidinediones, which target the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-g, have been reported recently to exhibit potent anti-inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and apoptosis.
- 2The present study was conducted to determine whether rosiglitazone, a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral infarction and neurological dysfunctions induced by embolic middle cerebral artery (MCA) occlusion in the rat.
- 3Focal ischaemic injury was induced by embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3 or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after embolization. Forty-eight hours after MCA occlusion, brains were removed, sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride and analysed using a commercial image-processing software program.
- 4When rosiglitazone was administered 1 h before embolization, it significantly reduced infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg, respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P < 0.001). Rosiglitazone-treated rats also demonstrated improved neurological functions. However, there were no statistically significant differences between control and treated groups in terms of brain oedema at 48 h after ischaemic injury.
- 5The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke.