Changes Of Hippocampal Mossy Fiber Sprouting And Rac1 RhoA Expressions In The PTZ Kindling Model

ObjectThis study is aimed to investigate the expression changes of Rac1and RhoA in every zonal of hippocampus associated with the changes of hippcampal mossy fiber sprouting in the pentylenetetrazole kindling and fasudil intervention model, and to investigate the role of Rho-GTPases and the Rho Signaling Pathway in mossy fiber sprouting procession, and to extrapolate the role of fasudil in epileptogenesis.Methods210 healthy male Sprague-Dawley rats were randomly divided into control group, PTZ kindling model treated group and fasudil treated group. The Rats of PTZ model group were intraperitoneally injected PTZ (30mg/kg) ever day and were stopped injection once kingdled. The ones of the fasudil treated group were intraperitoneally injected fasudil(15mg/kg) at firse,and then were injected PTZ (30mg/kg) about halfhour later. The control group received 0.9% saline injections instead of PTZ at the same time. Then every groups were randomly divided into seven subgroups according to 1d, 3d, 1w, 2w, 4w, 6w, 8w after the first PTZ injection.Timm staining were scored at different time in the CA3 region of hippocampus and dentate gyrus.The expression of Rac1 and RhoA were analyzed at diffferent time in the hilus and stratum granulosum of dentate gyrus by using immunohistichemistry method.Results1. Observation of epilepsia praxiology: There is no difference of seizure level, emergence time and kindled rate between PTZ and fasudil treated groups.2. Changes of hippocampal mossy fiber sproutingThe scores of Timm staining in the CA3 region were no significantly differences between PTZ and fasudil groups,but there were significantly higher than the control group.With daily PTZ application, the scores gradually increased from 3d to 2w,and maintained high levels up to 8w.There were no significantly differences in supragranular region among the PTZ and fasudil treated groups and the control group at different time points.3. The major expression of Rac1 and RhoA in control group rats lies on pyramidal cell and hilus fascia dentata.a) Rac1 expressionThe Rac1 expression levels of each trested group in CA3 and hilus were congruent. The expression incressed from 3d, and were significantly higher at 2w. Thereafter, the expression maintained high levels up to 6w(p<0.05), and then gradually decreased to the levels of 3d(p>0.05).b) RhoA expression The RhoA expression levels of each trested group in CA3 and hilus were congruent. The expression incressed from 1w to 4w, and maintained high levels at 6w(p<0.05). Thereafter, the expression decresed to the levels of 1w (p>0.05).ConclutionRac1 and RhoA may play a role in epileptogenesis by influencing mossy fiber sprouting. Fasudil has no obvious effect on the expression of Rac1 and RhoA, and no obvious effect on mossy fiber sprouting.