Combination Therapy of Rosiglitazone, a Peroxisome Proliferator‐Activated Receptor‐γ Ligand, and NMDA Receptor Antagonist (MK‐801) on Experimental Embolic Stroke in Rats

: 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