| Objective Epilepsy is a frequently-occurring chronic disease of the nervous system. The pathogenesis of epilepsy is mostly unknown. The relationship between inflammation and epilepsy have been studied by neurologists and scientists for several years. And immune reaction and its related factors has received wide attention. In this area, one of the most powerful inflammation factors-IL-1β, have been demonstrated in human brain specimens with epilepsy and epileptic animal models. There is compelling evidence that IL-1β is involved in increasing excitotoxicity. In this study, we established the lithium chloride-pilocarpine-induced SE model, explored that whether pharmacological administration of IL-1β could neutralize the abnormal high level of IL-1β induced by SE and to detect whether IL-1β antibody play an antiepileptic role through the regulation of inflammatory reactions.Method We chose 72 healthy adult male SD rats and randomly divided them into the control group(n=20), the SE group(n=26), and the anti-IL-1β group(n=26), the SE group and anti-IL-1β antibody treated group were injected with lithium chloride and pilocarpine. For the anti-IL-1β group, anti-IL-1β antibody was injected intraperitoneally at 30 minutes after the injection of pilocarpine and repeated at day 7 and day 14 post-SE. The control and SE group received the same volume of saline instead of anti-IL-1β antibody. Western blot was used to detect the antibody penetration in hippocampus at 72 h and 21 d post injection. At 72 h post injection, RT-PCR was used to detect the gene expression of IL-1β, NF-κB m RNA; ELISA was used to detect the serum level of S100 B. At 21 d post injection, immunological analysis of brain tissue was done to value the glial activation and nissl staining was done to observe the pathological changes of hippocampus.Result 1. 10-40 min after the injection of pilocarpine, SE group animals began to appear urination, defecation, salivation, bloodshot eyes, head nodding, locomotionunsteadiness, unbalance, facial and limbic convulsion, and then rats appeared generalized tonic-clonic seizures and transient loss of postural control. The success rate of epileptic molding was 85.29% and the death rate was 10.34%(58 epileptic rats with 68 normal rats, and 6 of epileptic models died within 48 h post pilocarpine injected). 2.IL-1β antibody passed BBB and kept therapeutic concentrations(>3.00 ug Ab/g). 3.The m RNA expression of IL-1β and NF-κB of the model group was higher than those of the sham group(P<0.01, respectively), and the m RNA expression of IL-1β and NF-κB of the IL-1β antibody-treatment group was lower than those of the model group(P<0.01, respectively). 4.The serum level of S100 B was very low, and compared with the model group, the serum level of S100 B of the IL-1β antibody-treatment group was significantly decreased(P<0.01). 5. Nissl stain revealed that pyramidal cells and neurons in hippocampus of the sham group was aligned and integrated. Significant loss of pyramidal cells and neurons in hippocampus was presented in the model group, while loss of those in the IL-1β antibody-treatment group was significantly decreased(P<0.01). Additionally repeated systemic administration of IL-1β antibody significantly attenuated the hippocampus glial activation caused by SE(P < 0.01).Conclusion 1. Inflammation and cytokines act as an important part to SE. 2. Intraperitoneally administration of IL-1β antibody passed BBB and kept therapeutic concentrations. Neutralizition the abnormal high level of IL-1βameliorated inflammatory reactions induced by SE and played an antiepileptic role. 3. The neutralization of IL-1β suggested a potential clinical benefit of therapeutic interventions. |
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