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

Brain Res. 2008 May 7:1208:240-9. doi: 10.1016/j.brainres.2008.02.007. Epub 2008 Feb 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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