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

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.

Neurogliovascular unit after cerebral ischemia: is the vascular wall a pharmacological target.

Ischemic stroke induces drastic alterations of the functions of the neurogliovascular unit with dramatic consequences on the well-being of the patients in terms of cognitive and motor handicap. Nowadays, only very few therapeutics are available as a treatment of ischemic stroke. Ischemia is a multifactorial pathology involving different cerebral cellular components such as neurons, astrocytes and vessels working as a functional unit. Recent experimental strategy investigation involving different agents with antioxidant properties (dt-BC, stobadine) or pleiotropic effects (lipopolysaccharide, LPS) has been developed to evaluate whether the vascular wall could be considered as a potential target in neuroprotection concept.