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Rafsanjan University of Medical Sciences

Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-γ ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats

(2007) Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-γ ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats. Basic and Clinical Pharmacology and Toxicology. pp. 309-314. ISSN 17427835 (ISSN)

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Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been found to have potent anti-inflammatory actions and suggested as potential therapies for brain ischaemia. Glutamate is the most common excitatory neurotransmitter in the central nervous system and is released excessively during ischaemia. Stroke therapy will require combinations of drug classes, because no single drug class has yet been proven efficacious in human beings. The present study was conducted to assess whether N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment can improve recovery from ischaemic brain injury and whether rosiglitazone, a PPAR-γ ligand, can increase its neuroprotective effect in an embolic model of stroke. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery. Rosiglitazone (0.1 mg/kg, intraperitoneally) and MK-801 (0.1 mg/kg, intravenously) were injected immediately after embolization. Forty-eight hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analysed by a commercial image processing software programme. Rosiglitazone and MK-801 alone or in combination decreased infarct volume by 49.16, 50.26 and 81.32, respectively (P < 0.001). Moreover, the combination therapy significantly decreased the infarct volume when compared to any drug used alone (P < 0.05). MK-801 reduced the brain oedema by 68 compared to the control group (P < 0.05), but rosiglitazone or combination did not show any significant effect. The drugs alone or in combination also demonstrated improved neurological function, but combination therapy was more effective on neurological deficits improving. Our data show that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone; this effect perhaps represents a possible additive effect in the brain infarction. © 2007 The Authors.

Item Type: Article
Keywords: benzene derivative dizocilpine rosiglitazone triphenyltetrazolum chloride unclassified drug animal experiment animal model animal tissue article artificial embolism blood clotting brain artery brain infarction brain injury brain region computer program controlled study embolism imaging male monotherapy neuroprotection nonhuman priority journal rat staining stroke Animals Behavior, Animal Blood Coagulation Brain Cerebral Infarction Dimethyl Sulfoxide Dizocilpine Maleate Drug Synergism Drug Therapy, Combination Hypnotics and Sedatives Intracranial Embolism Neuroprotective Agents PPAR gamma Rats Receptors, N-Methyl-D-Aspartate Thiazolidinediones Rattus
Page Range: pp. 309-314
Journal or Publication Title: Basic and Clinical Pharmacology and Toxicology
Journal Index: Scopus
Volume: 101
Number: 5
Identification Number: https://doi.org/10.1111/j.1742-7843.2007.00127.x
ISSN: 17427835 (ISSN)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/5402

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