Boer K, Spliet W G M, van Rijen P C, Redeker S, Troost D, Aronica E
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
J Neuroimmunol. 2006 Apr;173(1-2):188-95. doi: 10.1016/j.jneuroim.2006.01.002. Epub 2006 Feb 17.
Focal cortical dysplasia (FCD), which is caused by malformations of cortical development, is known to be a major cause of intractable epilepsy. Cortical laminar disorganization and the presence of abnormal neuronal and astroglial cell types are histological characteristics of FCD. Though, little information is known about the microglia/macrophage cell system in FCD and its possible contribution to the high epileptogenesis of this disorder. In the present study, the distribution of cells of the microglia/macrophage lineage was studied in 20 specimens of FCD (type II) by immunocytochemistry for CD68 and human HLA-DR. A significant number of microglial cells and macrophages were observed within the dysplastic cortex. The mean number of CD68- and HLA-DR-positive cells was significantly higher in FCD specimens than in normal-appearing control cortex obtained at autopsy. HLA-DR-positive cells, which represent activated microglia, were localized around blood vessels and also clustered around dysplastic neuronal cells. The density of these activated HLA-DR-positive microglial cells correlated with the duration of epilepsy, as well as with the frequency of seizures prior to surgical resection. CD68-positive macrophages were mainly located around vessels and the number of these cells did not correlate with seizure frequency, neither with the duration of symptoms prior to surgical resection. In conclusion, our findings demonstrate a specific and persistent increase in the numerical density of HLA-DR-positive activated microglia within the dysplastic region, supporting the contribution of the inflammatory response and proinflammatory molecules to the epileptogenicity of FCD.
局灶性皮质发育不良（FCD）由皮质发育畸形引起，是难治性癫痫的主要原因。皮质层状结构紊乱以及异常神经元和星形胶质细胞类型的存在是FCD的组织学特征。然而，关于FCD中的小胶质细胞/巨噬细胞系统及其对该疾病高癫痫易感性的可能作用，人们了解甚少。在本研究中，通过对CD68和人HLA - DR进行免疫细胞化学，研究了20例FCD（II型）标本中小胶质细胞/巨噬细胞谱系细胞的分布。在发育异常的皮质内观察到大量小胶质细胞和巨噬细胞。FCD标本中CD68和HLA - DR阳性细胞的平均数量显著高于尸检获得的外观正常的对照皮质。代表活化小胶质细胞的HLA - DR阳性细胞定位于血管周围，也聚集在发育异常的神经元细胞周围。这些活化的HLA - DR阳性小胶质细胞的密度与癫痫持续时间以及手术切除前的癫痫发作频率相关。CD68阳性巨噬细胞主要位于血管周围，这些细胞的数量与癫痫发作频率以及手术切除前的症状持续时间均无相关性。总之，我们的研究结果表明，发育异常区域内HLA - DR阳性活化小胶质细胞的数量密度有特异性和持续性增加，支持炎症反应和促炎分子对FCD癫痫易感性的作用。
