Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Epilepsia. 2010 Sep;51(9):1763-73. doi: 10.1111/j.1528-1167.2010.02547.x.
Induction of inflammatory pathways has been reported in epileptic patients with focal malformations of cortical development. In the present study we examined the innate and adaptive immune responses in focal cortical dysplasia (FCD) with different histopathologic and pathogenetic features.
The inflammatory cell components and the induction of major proinflammatory pathways and molecules [complement pathway, interleukin (IL)-1β, and chemokine monocyte chemotactic protein-1 (MCP1)] was investigated in surgical specimens of sporadic type IA and type IIB FCD using immunocytochemical methods.
FCD II but not FCD I cases exhibit activation of the mammalian target of rapamycin (mTOR) cascade with strong neuronal expression of the phosphorylated isoform of S6 protein. Microglia reactivity was increased in all lesions (FCD I and II) compared to control tissue; however, the number of HLA-DR-positive cells was significantly higher in FCD II than in FCD I. In FCD II specimens we also observed perivascular and parenchymal T lymphocytes (CD3(+) ), with a predominance of CD8(+) T-cytotoxic/suppressor lymphocytes, as well as a few dendritic cells. Expression of components of the complement cascade, IL-1β, and MCP1 was prominent in FCD II cases.
Our findings indicate a prominent activation of both innate and adaptive immunity, with involvement of different inflammatory pathways in FCD II cases, supporting the possible involvement of inflammation in the epileptogenesis of these lesions, as well as the notion that FCD II is pathologically distinct from FCD I.
据报道，在伴有皮质发育畸形的癫痫患者中存在炎症途径的诱导。在本研究中，我们检查了具有不同组织病理学和发病机制特征的局灶性皮质发育不良（FCD）中的固有和适应性免疫反应。
使用免疫细胞化学方法，研究了散发性 FCD IA 型和 FCD IIB 型手术标本中炎症细胞成分以及主要促炎途径和分子（补体途径、白细胞介素（IL）-1β和趋化因子单核细胞趋化蛋白-1（MCP1））的诱导。
FCD II 型而非 FCD I 型病例表现出哺乳动物雷帕霉素靶蛋白（mTOR）级联的激活，磷酸化 S6 蛋白的同种型在神经元中表达强烈。与对照组织相比，所有病变（FCD I 和 FCD II）中的小胶质细胞反应性均增加；然而，FCD II 中的 HLA-DR 阳性细胞数明显高于 FCD I。在 FCD II 标本中，我们还观察到血管周围和实质 T 淋巴细胞（CD3(+)），以 CD8(+)T 细胞毒性/抑制性淋巴细胞为主，还有少数树突状细胞。补体级联、IL-1β和 MCP1 的表达在 FCD II 病例中明显。
我们的发现表明固有免疫和适应性免疫均明显激活，FCD II 病例涉及不同的炎症途径，支持炎症可能参与这些病变的癫痫发生，并且 FCD II 在病理学上与 FCD I 不同。
