Stobadine protects against ischemia-reperfusion induced morphological alterations of cerebral microcirculation in dogs

Vascular diseases of the CNS are a major medical, social and economic problem. From the number of causes leading to nervous malfunction and damage, ischemia is most prominent. Thus, neuronal protection from ischemic damage may provide significant preventive and treatment potential. This study was designed to test possible protective effects of stobadine in a canine model of global cerebral ischemia. Seven minute ischemia was induced by four vessel ligation and maintained using a controlled systemic hypotension. Stobadine pretreated animals were infused with 2 mg/kg stobadine 30 minutes prior to ischemia, while control animals received vehicle. After a 24 hour reperfusion phase, animals were perfusion-fixed and evaluated using electron microscopy. Stobadine pretreated dogs showed much less damage to both endothelial lining and pericapillary structures of the blood-brain barrier. This included preservation of cellular shape of the endothelium, patency of microvessels, lack of intraluminal blebs material, near normal cytoplasmic osmiophilia, decreased thickness of endothelial basement membrane, significantly less edema of astrocyte end-feet, and preservation of fine mitochondrial structure compared to the control group. Ischemic neuronal changes were observed less frequently in the stobadine pretreated group. In summary, we conclude that stobadine protects both cerebral microcirculation and neurons from injury induced by global cerebral ischemia and reperfusion.