Stobadine-induced hastening of sensorimotor recovery after focal ischemia/reperfusion is associated with cerebrovascular protection.

Abstract

In a model of 1 hour-intraluminal occlusion of rat middle cerebral artery (MCA), we investigated the spontaneous recovery of vascular functions and functional deficit together with ischemia volume evolution at 24 h, 3 days and 7 days of reperfusion. Infarct cerebral volumes and edema were quantified with histological methods. Endothelium-dependent and smooth muscle potassium inward rectifier current (Kir2.x)-dependent relaxing responses of MCA were tested using Halpern arteriograph and Kir2.x current density evaluated on MCA myocytes with whole-cell patch-clamp technique. Sensorimotor recovery was estimated according to performances obtained with adhesive removal test and prehensile traction test. A time-dependent improvement of smooth muscle K(+)-dependent vasorelaxation and Kir2.x current density is observed at 7 days of reperfusion while endothelium-dependent relaxation is still impaired. In parallel a significant reduction of functional deficit is observed at 7 days of reperfusion together with a time-matched reduction of striatal infarct and edema volumes. Administration of an antioxidant agent, stobadine, at time of reperfusion and 5 h later allowed: (i) a neuroprotective effect with a significant reduction of infarct size compared to vehicle-treated rats; (ii) a prevention of endothelial-dependent relaxation and Kir2.x current density reductions of MCA ipsilateral to occlusion; (iii) a hastening of the functional recovery. The beneficial effect of stobadine underlines a link between vascular protection, neuronal protection and sensorimotor recovery that could become a promising pharmacological target in the treatment of cerebral ischemia.

• Authors: F Plaisier, M Bastide, T Ouk, O Pétrault, M Laprais, S Stolc, R Bordet
• Journal: Brain research (Brain Res) Vol. 1208 Pg. 240-9 (May 07 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18377875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Carbolines
• Potassium Channels, Inwardly Rectifying
• Acetylcholine
• dicarbine

Topics

• Acetylcholine (pharmacology)
• Analysis of Variance
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Brain Edema (etiology, prevention & control)
• Carbolines (pharmacology, therapeutic use)
• Cerebral Infarction (etiology, prevention & control)
• Cerebrovascular Circulation (drug effects)
• Disease Models, Animal
• Male
• Membrane Potentials (drug effects, physiology)
• Muscle, Smooth (drug effects, physiopathology)
• Patch-Clamp Techniques
• Potassium Channels, Inwardly Rectifying (physiology)
• Psychomotor Performance (drug effects)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, pathology, physiopathology)
• Time Factors
• Vasodilation (drug effects)