Paper Information

Title:  COMBINATION THERAPY OF MK-801 AND ROSIGLITAZONE (A PPAR-Γ LIGAND) IN EXPERIMENTAL THROMBOEMBOLIC STROKE IN RATS
Type: SPEECH
Author(s): ALAH TAVAKOLI M.,SHABANZADEH A.R.,ROUHBAKHSH A.,POURSHANAZARI A.A.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Glutamate is the most common excitatory neurotransmitter in the CNS and is released excessively during ischemia. Elevated extracellular glutamate after cerebral ischemia is thought to play a key role in the development of cerebral infarction via N-methyl-D-aspartate (NMDA) receptors. Stroke therapy will require combinations of drug classes because no single drug class has yet been proven efficacious in humans. The present study was conducted to assess whether NMDA receptor antagonist treatment can improve recovery of ischemic brain injury and whether rosiglitazone a PPAR-γ ligand can increase its neuroprotective effect in an embolic stroke model. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery (MCA). Rosiglitazone (0.1 mg/kg, i.p.) and MK-801 (0.1 mg/kg, i.v.) were injected immediately after embolization. 48 hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analyzed by a commercial image processing software program. Rosiglitazone and MK-801 either 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 infract volume when compared to any drug used alone (P<0.05). MK-801 reduced the brain edema 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 showed that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone and this effect may represent a merely additive interaction.

 
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