Inflammatory pathways control role in epileptogenic neuronogenesis

癫痫发作引起持续的病理学和电生理学的海马区（HIPP）变化，诱导癫痫发生（EG）。到目前为止还没有发现对这一过程的控制。为了对诱导的EG进行药理学控制，我们评价了左乙拉西坦（LEV）对癫痫小鼠HIPPi病理变化的治疗作用，其中连续LEV治疗抑制癫痫诱导的神经发生。预防性LEV治疗可能抑制这种病理变化。然而，EG诱导的细胞和分子机制仍不清楚。脑炎症机制激活作为获得性EG的一个因素近年来受到广泛关注。我们的初步临床研究表明，HMGB 1和TLR 4的表达升高，表明HMGB 1-TLR 4通路参与人类EG。在人EG HIPP中，HMGB 1参与TLR 4的表达，可能与HIPP的硬化诱导（CA 1> DG> CA 2）和萎缩有关，

Epileptic seizures cause continuous pathological and electrophysiological hippocampul (HIPP) changes, inducing epileptogenesis (EG). Control of this process has not been found until now. Aiming pharmacological control on induced EG, we evaluated treatment effect of levetiracetam (LEV) on pathological changes in epileptic mice HIPPi where continuous LEV treatment suppressed epilepsy-induced neurogenesis. Preventive LEV treatment potentially inhibits such pathological changes. Cellular and molecular mechanisms of EG induction, however, remain unclear. Brain inflammatory mechanisms activation received recently broad attention as a factor in acquired EG. Our preliminary clinical study suggested elevated expression of HMGB1 and TLR4 in sclerotic HIPPi, indicating HMGB1-TLR4 pathway involvement in human EG. More, in human EG HIPP, HMGB1 involved consequently TLR4, probably in relation to HIPP sclerosis induction (CA1> DG> CA2) and atrophy,