Icariside II improves cerebral microcirculatory disturbance and alleviates hippocampal injury in gerbils after ischemia–reperfusion

Abstract Objective : the purpose of the present study was to examine the protective effect of Icariside II (IS) on cerebral microcirculatory disturbance and neuronal injury in hippocampal CA1 region induced by global cerebral I/R and the underlying mechanism. Methods : male Mongolian gerbils (50–70 g) were subjected to bilateral common carotid arteries occlusion for 30 min and followed by reperfusion for 72 h. IS (20 mg/kg) was administered orally 2 h before ischemia and 6, 24, 48, 70 h after reperfusion. After 72 h of reperfusion, the leukocyte adhesion, albumin leakage, and velocity of RBC in the venules were determined with an upright microscope. Neuronal injury in hippocampal CA1 region was assessed by Nissl staining and the in situ TUNEL assay. Bax, Bcl-2, and cleaved caspase-3 proteins were detected by Western blot, and MDA content and complex I activity by ELISA assay in hippocampus. Results : IS inhibited I/R-elicited leukocyte adhesion, albumin leakage and increased the velocity of RBC in cerebral venules. IS down-regulated Bax and cleaved caspase-3 expression, up-regulated Bcl-2 expression of hippocampus and decreased the number of TUNEL positive neurons and the neuronal loss induced by I/R in hippocampal CA1 region. In addition, IS could increase the activity of complex I and decrease the production of MDA after I/R. Conclusions : IS could alleviate the microcirculatory disturbance and neuronal injury in hippocampal CA1 region induced by global cerebral I/R, which might involve regulating complex I activity.