Effects Of Rapamycin,Inhibitor Of MTOR Signaling Pathway,on Neonatal Seizures In Rats

Objective:Neonatal period is the most vulnerable time for the occurrence of seizures, and neonatal seizures often pose a clinical challenge both for their acute management and frequency of associated long-term comorbidities. Therefore,finding the way to reduce seizure of infants and control the disease effectively,is a pressing clinical problem. Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. The mammalian target of rapamycin (mTOR) signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in many types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy, and acquired temporal lobe epilepsy following brain injury, but these effects depend on a high dose of conditions.Whether a lower dose of rapamycin-treatment can play a similary role as the higher dose do for epilepsy?In the present study,we explored short-and long-term outcomes followed neonatal seizures,and a lower dose of rapamycin-treatment whether play the same role as high dose do.Methods:We explored short- and long-term consequences of neonatal pilocarpin-induced seizures in 10 day old SD rats. Protein marker of mTOR signaling pathway was detected by western blot.DCX fluorescent staining was used to measure the number of DCX positive cells.Timm staining was used to detected the mossy fiber sprouting.The immune factor expression level was test by Elisa.And behavior change of each group was test by behavior test.Results:mTOR pathway was activated in the short-and long-term test after neonatal seizures.and treatment of low dose rapamycin may reverse those changes.Neonatal seizures can induce DCX cells and mossy fiber sprouting increased.Immune factors were increased at 24h and 3days after neonatal seizures.Neonatal seizures may induce rats be more anxiety,and rapamycin administration can reverse this situation.Conclusions:mTOR pathway is activated followed neonatal seizures in acute and chronic phase in rats.Treatment of low dose rapamycin may induce or even eliminate epilepsy.