To observe the effect of IcarisideⅡ(ICSⅡ) on spatial learning and memory impairments and axonal regeneration induced by chronic cerebral hypoperfusion(CCH) in rats.

90 male SD rats were randomly divided into normal group, sham operation group, CCH group and ICSⅡ low, middle and high-dose treatment groups.The chronic cerebral hypoperfusion model was established by permanent bilateral common carotid artery occlusion.Then these rats in ICSⅡ low, middle and high-dose treatment groups were given ICSⅡ4, 8 and 16 mg/(kg·d) by gavage on the 1st day after modeling.There were 5 rats in every group at each observing time(4, 8 and 12 week). Morris water maze experiment was utilized to assess the escape latency and the target quadrant residence time while HE and immunohistochemistry analysis were applied to test the morphology change and expressions of GAP-43, MAP-2 and Nogo-A in hippocampal CA1.

Compared with those of sham operation groups at 4, 8 and 12 week respectively, the escape latency in CCH group were significantly prolonged(40.02±4.95)s, (42.29±5.75)s, (53.68±6.14)s vs (26.43±2.68)s, (26.84±2.06)s, (31.53±4.12)s, P<0.05; the target quadrant residence time were significantly reduced(28.53±2.40)s, (28.02±4.28)s, (22.60±4.03)s vs (33.34±2.89)s, (33.31±4.14)s, (31.63±2.20)s, P<0.05); the expressions of GAP-43 and Nogo-A were increased with that of MAP-2 reduced(P<0.05). Meanwhile, the neuropathological changes with more denatured neurons and less normal neurons were found in hippocampal CA1.However, compared with those of CCH group, the escape latency of ICSⅡ middle and high-dose groups (30.58±3.03)s, (29.19±4.23)s, (38.77±5.80)s; (28.90±2.98)s, (26.91±6.63)s, (36.51±3.98)s) were shortened (P<0.05); the target quadrant residence time(32.54±3.41)s, (32.69±3.47)s, (28.27±3.57)s; (32.69±3.54)s, (33.20±4.29)s, (28.07±4.04)s) were increased (P<0.05); the expression of Nogo-A was decreased while those of GAP-43 and MAP-2 were conversely increased (P<0.05). Moreover, few denatured neurons were observed in hippocampal CA1.But there were no differences for those indexs between CCH group and ICSⅡ low-dose treatment groups(P>0.05). Compared with those in 8 week and 4 week, the escape latency and the target quadrant residence time were prolonged and reduced with the expression of Nogo-A increased in all groups except normal group and sham operation group(P<0.05), the expressions of GAP-43 and MAP-2 were decreased in CCH group and ICSⅡ low-dose treatment group(P<0.05), but there were no significant differences in ICSⅡ middle and high-dose treatment groups at 12 week(P>0.05). However, there were no statistical significance of all indexes between 8 week and 4 week(P>0.05).

ICSⅡ can improve the spatial learning and memory in chronic cerebral hypoperfusion rats, which may be achieved by neuroprotective effects and reducing the expression of Nogo-A consequently promotes the regeneration of axons.

IcarisideⅡ; Chronic cerebral hypoperfusion; Spatial learning and memory impairments; Axonal regeneration; Rat