The Effect Of Topiramate On The BFGF Expression And Mossy Fiber Sprouting With A Chronic Epilepsia Rat Model

1 Objective The study is aim to determine whether topiramate(TPM) has an effect on bFGF expression in hippocampus and moss fiber sprouting(MFS) in dentate gyrus with a chronic kindling rat model by pentetrazole(PTZ). 2 Methods To establish a chronic kindling rat model by pentetrazole and divide animals into three groups: (1)PTZ group: kindling rats, without therapy of topiramate; (2)TPM group: kindling rats, with therapy of topiramate; (3)N group: normal group. Then divide each group into next three groups at the time point of 5d,10d,15d when to observe bFGF expression by immunohistochemistry method and next two groups at the time point of 10d,15d when to observe MFS by Timm staining. HE staining is used to observe cellular morphologic change. 3 Results (1) Observation of epilepsia praxiology: There is no difference of seizure level,emergence time and kindled rate between PTZ and TPM groups. (2) Cellular morphologic change: In PTZ and TPM groups, many neurons are founded degenerated or necrosed in CA1 and CA3 areas of hippocampus especially in CA1 area,which is more obvious in PTZ group. (3) bFGF expression: bFGF expression is increased in hippocampus induced by pentetrazole especially in CA1 area. â‘ bFGF expression of each group at different time points: PTZ group, has a total increasing trend by time. In dentate gyrus, 10d and 15d groups are more increased compared with 5d group(p<0.05). In CA1 area, different time points are differed significantly(p<0.01). There is no difference in CA3 area. TPM group, has a total increasing trend by time in dentate gyrus and 10d ,15d groups are more increased compared with 5d group(p<0.05). But it shows a total decreasing trend by time in CA1 area The Effect of Topiramate on the bFGF Expression and Mossy Fiber Sprouting with a Chronic Epilepsia Rat Model Abstract and 10d,15d groups are more decreased compared with 5d group(p<0.01). In CA3 area, 10d group is more increased compared with 10d and 15d groups(p<0.05). There is no difference between each time point of normal group. â‘¡bFGF expression at the same time point in different groups: In dentate gyrus, PTZ and TPM groups are more increased compared with normal group at each time point(p<0.01). In CA1 area, PTZ and TPM groups are more increased compared with normal group at 5d(p<0.01). Only PTZ group is more increased compared with TPM and normal groups at 10d and 15d(p<0.01). In CA3 area, there is no difference at 5d. PTZ and TPM groups are more increased compared with normal group at 10d(PTZ group: p<0.01; TPM group: p<0.05). Only PTZ group is more increased compared with TPM and normal groups at 15d(p<0.01). (4) MFS is founded in both PTZ and TPM group in dentate gyrus, but there is no statistics difference between TPM and N group. 4 Conclusions (1)bFGF expression is increased in hippocampus during kindling process by pentetrazole especially in CA1 area,and has a increasing trend by time. Topiramate can decrease bFGF expression obviously in CA1 and CA3 areas of hippocampus. (2)Pentetrazole induces moss fiber sprouting in dentate gyrus. However, topiramate has no obvious effect on MFS before fully kindled(15d). (3)Neuron lesions are founded in hippocampus during kindling process by pentetrazole, especially in CA1 area. Topiramate has an protective effect to relieve neuron lesions during kindling process but have nothing to do with the anti-epilepsy role. (4)Topiramate may down-regulate bFGF expression by decreasing neuron lesions in hippocampus. (5)Topiramate has no effect on the process before fully kindled(15d)with a kindling model by pentetrazole.