Effect Of Intranasal Administration Of Levetiracetam On The Temporal And Spatial Distribution Of SV2A In The Amygdala-kindling Epileptic Rats

Objective: To verify that nasal delivery of LEV is effective;to observe the temporal and spatial distribution of SV2A in hippocampus of the amygdala-kindling epileptic rats and the effect of LEV nasal delivery on it.Methods: The rats were randomly divided into sham operation group(Sham),epilepsy group(EP),LEV oral administration group(LPO)and LEV nasal delivery group(LND).HE staining was used to observe the pathological changes of hippocampus in different periods of epilepsy.The amygdala-kindling epilepsy model of rats was established,and the pathological changes in hippocampal CA1 and CA3 areas of the LND group,LPO group,EP group and Sham group were compared 24 h and 3d after SE.Western blot was used to detect the expression of SV2A in the hippocampus of rats in the LND group,EP group and Sham group 1w,2w,and 4w after SE,and the change trend of SV2A expression after nasal administration of LEV.Immunofluorescence double labeling was used to detect the expression and distribution characteristics of SV2A at the above time points after SE in the EP group,LND group and Sham group.Results:(1)Compared with the Sham group,rats in the EP group showed obvious cell loss and tissue necrosis in the hippocampal CA3 area 1 day after SE,and the degree of tissue damage was more severe at 3 days after SE;The degree of tissue damage in the rats in the LPO and LND groups 1 and 3 days after SE was significantly reduced compared with EP group.Scattered cell loss was observed in hippocampal CA1 area of rats in each group at 1and 3 days after SE,and no significant difference was observed in the degree between each group.(2)Western Blot semi-quantitative measurement results showed that 1w after SE,hippocampal SV2A expression in EP and LND groups decreased,lower than that of sham operation group(P<0.05),and expression increased at 2w after SE,which was similar to the Sham group(P>0.05),the expression of 4w after SE continued to rise,higher than the Sham group(P<0.05);there was no significant difference in the expression of SV2A between the EP group and the LND group(P>0.05).(3)The results of immunofluorescence showed that 24 h after SE,the expression of SV2A in hippocampal CA3 area of EP and LND group was similar to that of sham operation group,and 1w after SE,the expression of SV2A in hippocampus CA3 area of EP and LND group was lower than that of sham operation.SV2A expression in hippocampus CA3 area increased 2w after SE,similar to sham operation group.SV2A expression in hippocampus CA3 area continued to rise 4w after SE,which was higher than that of sham operation group;no significant changes were observed in CA1 area SV2A expression.Conclusion:(1)The route of nasal administration of LEV and the route of oral administration exerted the same anti-epileptic and neuron protective effects.(2)During the incubation period of epilepsy,the total expression of SV2A in hippocampus decreased;the total expression of SV2A increased in the chronic phase.(3)During the incubation period of epilepsy,the expression of SV2A in the hippocampal CA3 area decreased,and the expression of SV2A in the hippocampal CA3 area increased in the chronic phase;the expression of SV2A in the hippocampus CA1 area did not change significantly.(4)LEV does not exert its efficacy by changing the expression of SV2A.