Abnormal migration of subventricular zone (SVZ)-derived neural progenitor cells (SDNPs) is involved in the pathological and epileptic processes of focal cortical dysplasias (FCDs), but the underlying mechanisms are not clear. Recent studies indicated that high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) are widely expressed in epileptic specimens of FCDs, which suggests that the HMGB1-RAGE pathway is involved in the pathological and/or epileptic processes of FCDs. The present study used Nestin-GFP^tg/+ transgenic mice, and we established a model of freezing lesion (FL), as described in our previous report. A “migrating stream” composed of GFP-Nestin⁺ SDNPs was derived from the SVZ region and migrated to the cortical FL area. We found that translocated HMGB1 and RAGE were expressed in cortical lesion in a clustered distribution pattern, which was especially obvious in the early stage of FL compared to the sham group. Notably, the number of GFP-Nestin⁺ SDNPs within the “migrating stream” was significantly decreased when the HMGB1-RAGE pathway was blocked by a RAGE antagonist or deletion of the RAGE gene. The absence of RAGE also decreased the activity of pentylenetetrazol-induced cortical epileptiform discharge. In summary, this study provided experimental evidence that the levels of extranuclear HMGB1 and its receptor RAGE were increased in cortical lesion in the early stage of the FL model. Activation of the HMGB1-RAGE pathway may contribute to the abnormal migration of SDNPs and the hyperexcitability of cortical lesion in the FL model.

脑室下区 (SVZ) 衍生的神经祖细胞 (SDNPs) 的异常迁移参与了局灶性皮质发育不良 (FCDs) 的病理和癫痫过程，但其潜在机制尚不清楚。最近的研究表明，高迁移率族盒 1 (HMGB1)/晚期糖基化终产物 (RAGE) 受体在 FCD 的癫痫标本中广泛表达，这表明 HMGB1-RAGE 通路参与了癫痫的病理和/或癫痫过程。 FCD。本研究使用 Nestin-GFP ^tg/+转基因小鼠，我们建立了冷冻病变 (FL) 模型，如我们之前的报告中所述。^{由 GFP-Nestin +}组成的“迁移流”SDNPs 来源于 SVZ 区域并迁移到皮质 FL 区域。我们发现易位的HMGB1和RAGE在皮层病变中呈聚集分布模式，与假手术组相比，在FL早期尤其明显。值得注意的是，当 HMGB1-RAGE 通路被 RAGE 拮抗剂阻断或 RAGE 缺失时，“迁移流”中 GFP-Nestin + SDNP的数量^显着减少基因。RAGE 的缺乏也降低了戊四唑诱导的皮质癫痫样放电的活性。综上所述，本研究提供的实验证据表明，在 FL 模型早期，皮层病变中核外 HMGB1 及其受体 RAGE 水平升高。HMGB1-RAGE通路的激活可能导致FL模型中SDNPs的异常迁移和皮质病变的过度兴奋。