Inflammatory pathways control role in epileptogenic neuronogenesis

癫痫发作引起海马神经元(HIPP)持续的病理和电生理改变，导致癫痫发生。到目前为止，还没有找到对这一过程的控制。为了对癫痫诱发的脑电进行药理控制，我们评价了左乙拉西坦(Lev)对癫痫小鼠海马神经细胞分化的治疗作用。预防性的LEV治疗有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。近年来，脑部炎症机制的激活作为获得性脑震荡的一个因素受到广泛关注。我们的初步临床研究表明，HMGB1和TLR4在硬化性河马中的表达增加，表明HMGB1-TLR4通路参与了人类EG。此外，在人类EG Hipp中，HMGB1随后涉及TLR4，可能与Hipp硬化诱导(CA1&GT；DG&GT；CA2)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,