title: Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces infarction volume and neurological deficits in an embolic model of stroke.
abstract: 1. Stroke 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. 2. The 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. 3. Focal 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. 4. When 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. 5. The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke.
authors.affiliation: Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Allahtavakoli
authors.forename: Alireza P
authors.initials: AP
authors.lastname: Shabanzadeh
authors.forename: Seyed Shahabeddin
authors.initials: SS
authors.lastname: Sadr
authors.forename: Mohsen
authors.initials: M
authors.lastname: Parviz
authors.forename: Bijan
authors.initials: B
authors.lastname: Djahanguiri
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001929:Brain Edema / Q000188:drug therapy; D020520:Brain Infarction / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D000077154:Rosiglitazone; D020521:Stroke / Q000188:drug therapy*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone