Objective      To determine the effect of cyclosporine A (CsA) on blood-brain barrier after cerebral ischemia-reperfusion (I/R) injury in mice and investigate its possible mechanism.       Methods      Middle cerebral artery occlus

ion (MCAO) model were established by Longa’s method in C57 BL/6J mice and apolipoprotein E knockout (ApoE

-/-

) mice. Then the C57BL/6J mice and  ApoE

-/-

mice were assigned into 5 groups

that is

sham operation group (n=5)

I/R group (n=14)

vehicle group (n=14)

low- and high- dose CsA intervention groups (10 and 20 mg/kg

given intraperitoneally in 15 min

and 24 and 48 h after model establishment

n=14). After neurological function was evaluated

the mice were sacrificed in 1

3

5 and 7 d after surgery

and the brain tissues were harvested for infarct volume

brain water content

and the permeability of blood-brain barrier (Evans blue leakage). Western blotting was used to detect the expression levels of p-Akt and Claudin-5.       Results       (1) Neurological function evaluation showed that MCAO resulted in severe neurological dysfunction in the mice

but CsA intervention obviously attenuated the injury

with the high-dose group superior to the low-dose group (P0.05). (2) Cerebral I/R injury induced severe cerebral edema

cerebral infarction and reduced leakage of blood-brain barrier

and the ApoE

-/-

mice were injured more heavily than the C57 mice (P0.05). However

CsA alleviated the symptoms

and the effects were more significant in the high- than low-dose intervention group (P0.05). (3) Western blot results showed that the protein level of p-Akt was higher

while that of Claudin-5 was lower in the brain tissue of normal ApoE

-/-

mice than normal C57BL/6J mice (P0.05). After MCAO

the expression of p-Akt was significantly increased and then Claudin-5 was decreased (P0.05). CsA inhibited the process

and the high-dose group had greater effect than the low-dose group (P0.05).       Conclusion      CsA repairs the blood-brain barrier damage induced by I/R injury

and then improves the prognosis

which is related with PI3K/Akt signal pathway. Besides

ApoE

-/-

mice have more severe cerebral infarction through this signal pathway.