Eeffects Of Ag490 On Reactive Astrocytes Following Lithium-pilocarpine-induced Rat Seizures

Objective: To investigate the spatiotemporal distribution pattern of tumor necrosis factor (TNF-α) and reactive astrocytes in rats hippocampus following p Lithium-pilocarpine-induced seizures,and to infer the role of JAK/STAT signaling pathway in gliosis of rats with epilepsy.Methods: Temporal lobe epilepsy models were established on rats by intraperitoneal injection of Lithium-pilocarpine (PILO) , and specific JAK/STAT inhibitor-AG490 was used to set up pretreated models,and saline was injected in the normal control group. The expression pattern of TNF-αprotein and astrocytes was were measured and compared in each group with western blotting and double immunofluorescence assay before and after blockage of the JAK/STAT pathway in rat presented seizures hippocampus. Results:1. Behavior in rats: No seizures onset were observed in the Saline control group .Among the Lithium-pilocarpine -treated rats, 80.00%(34/40) of animals up to gradeⅣand above attack Racing , 10.10%(4/40) of male rats died, and 10.10%(4/40) of male rats below the gradeⅣclass attack Racing were expelled,Model of success rate was 90.00%, 30 days, the group still has two spontaneous seizures, and 25.00% (2 / 8).AG490 intervention groups of male rats,Ⅳlevel and above attack rate was 75.00%(30/40),mortality rate was 17.50%(7/40) and 2.50% were expelled, Accounted for 23 to V-class attack only 76.67% (23/30) 30-day group, there is still a spontaneous attack, and 12.50% (1 / 8),Ⅳlevel and below onset epilepsy model induced with PILO group P < 0.05; other P> 0.05.2. western blotting: PILO model group, tumor necrosis facto(rTNF-α)-alpha in seizures 3 hours after compared with saline control group,which began to increase, seizures reached a peak on day 3,then decreased gradually,The first 30 days of oneset of seizures to the protein level was still slightly higher than normal.AG490 intervention groups at each time point the expression of TNF-αsignificantly reduced compared with PILO group. 3h group, 12h respectively, and 24h, 3d group significantly different compared to p <0.01,30 d epilepsy still have seizures group and 30d do not attack groups was not significant( P> 0.05)3. Double Immunoflourescence Assay: A yellow-green particles were positive staining, positive cell can be seen in the astrocytes of the spatial distribution, AG490 intervention groups,positive granules of astrocytes were significantly reduced,(P<0.05). JAK/STAT pathway can promote the proliferation of astrocytes.Conclusion: limhium-pilocarpine epilepsy model on rats can reproduce human temporal lobe epilepsy similarly, whatever of behavior changes or pathological changes.In the early seizures,Proliferation of astrocytes in hippocampus cells can be regarded that seizures lead to neuronal injury in an adaptive response,but go there late ,may promote further seizures of epilepsy, AG490 can block the JAK/STAT signaling pathway and inhibit proliferation of astrocytes,And also can change the behavior and the reactive gliosis, AG490 reduce the oneset of epilepsy with the inhibition effects on the Proliferation of astrocytes.