Abstract: Objective To investigate the neuroprotective effects of histone deacetylases(HDACs) inhibitor 11r on rats after seizures. Methods A total of 40 rats were randomly divided into 5 groups: control group,pilocarpine group, treatment group I(administered with 11r, 2.5 mg/kg, once a day,intraperitoneally in three consecutive days), treatment group Ⅱ(administered with 11r, 25 mg/kg, once a day, intraperitoneally in three consecutive days), and 11r pretreatment group. Lithium chloride and pilocarpine were used to induce status epilepticus. The behaviors of rats in each group were observed. HE staining was performed to detect neuronal degeneration in hippocampus 24 hours after pilocarpine-induced seizure. At 72 hour after seizures, Nissl staining and immunohistochemical staining were used to evaluate the loss of neurons and histone acetylation levels of hippocampal CA1 and CA3 regions in each group. Results Compared with pilocarpine group, 11r pretreatment group showed delayed pilocarpine-induced seizures and reduced mortality (P<0.05). Compared with those in pilocarpine group, the degrees of neuronal loss and degeneration in both treatment group Ⅰ and Ⅱ reduced (P<0.05), and the levels of histone acetylation in hippocampal CA1 and CA3 regions increased (P<0.05),while, the difference was not statistically significant between treatment group Ⅰ and Ⅱ (P>0.05). Conclusion New HDACs inhibitor 11r can improve pathological changes and histone acetylation levels of the brain in rats in the acute phase of pilocarpine-induced status epilepticus, which exerts neuroprotective effects on rats after seizures.

Key words: Hippocampus, Neuroprotection, Anticonvulsant, Seizures, Histone acetylation