Characterization of nodular neuronal heterotopia in children
Characterization of nodular neuronal heterotopia in children
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DOI：
10.1093/brain/122.2.219
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发表时间：
1999-02-01
期刊：
影响因子：
14.5
通讯作者：
Molnár, Z
中科院分区：
文献类型：
--
作者：
Hannan, AJ;Servotte, S;Molnár, Z
神经元异位可见于各种病理，并与顽固性癫痫有关。我们检查了四名患有不同病因的皮质下或脑室周围结节性异位的儿童的脑组织：一名在妊娠 17 周时局灶性脑外伤后患有严重癫痫，一名患有半脑畸形和顽固性癫痫，一名患有局灶性皮质发育不良和顽固性癫痫，以及一名患有相关脑积水和多小脑回的畸形足月婴儿。使用组织学和碳青染料 (DiI) 示踪技术研究结节的连通性。 DiI 晶体放置在异位结节附近，在晶体的 2-3 mm 半径内显示出许多 DiI 标记的纤维。尽管我们观察到标记纤维紧密围绕结节，但大多数并未穿透它们。将 DiI 晶体放置在结节内还发现了结节外的有限数量的突出物，并且在一种情况下，有证据表明相邻结节之间存在连通性。还使用免疫组织化学检查了结节的细胞和神经化学成分的钙结合蛋白和神经肽 Y (NPY)，它们通常在 GABA 能皮质中间神经元中表达。在所有病例的异位结节中，均鉴定出大量钙结合蛋白阳性神经元，以及一些细胞体和许多 NPY 阳性突起。结节内的钙结合蛋白阳性神经元在形态上不如皮质中的复杂，这可能反映了不完全分化为抑制性神经元表型。在覆盖的皮质板中也存在异常的钙结合蛋白阳性细胞簇，表明产生异位结节的迁移缺陷也会影响皮质本身的发育。因此，由多种神经元细胞类型组成的异位结节与上层皮质板的畸形相关，并且与其他大脑区域的连接有限。这种连接的异常发展可能会影响神经元的成熟，从而影响神经元回路中兴奋和抑制的平衡，从而导致其致癫痫的可能性。
Neuronal heterotopia are seen in various pathologies and are associated with intractable epilepsy. We examined brain tissue from four children with subcortical or periventricular nodular heterotopia of different aetiologies: one with severe epilepsy following focal brain trauma at 17 weeks gestation, one with hemimegalencephaly and intractable epilepsy, one with focal cortical dysplasia and intractable epilepsy, and one dysmorphic term infant with associated hydrocephalus and polymicrogyria. The connectivity of nodules was investigated using histological and carbocyanine dye (DiI) tracing techniques. DiI crystal placement adjacent to heterotopic nodules revealed numerous DiI-labelled fibres within a 2-3 mm radius of the crystals. Although we observed labelled fibres closely surrounding nodules, the majority did not penetrate them. Placement of DiI crystals within nodules also identified a limited number of projections out of the nodules and in one case there was evidence for connectivity between adjacent nodules. The cellular and neurochemical composition of nodules was also examined using immunohistochemistry for calretinin and neuropeptide Y (NPY), which are normally expressed in GABAergic cortical interneurons. Within heterotopic nodules from all cases, numerous calretinin-positive neurons were identified, along with a few cell bodies and many processes positive for NPY. Calretinin-positive neurons within nodules were less morphologically complex than those in the cortex, which may reflect incomplete differentiation into an inhibitory neuronal phenotype. There were also abnormal clusters of calretinin-positive cells in the overlying cortical plate, indicating that the migratory defect which produces heterotopic nodules also affects development of the cortex itself. Thus, heterotopic nodules consisting of multiple neuronal cell types are associated with malformation in the overlying cortical plate, and have limited connectivity with other brain regions. This abnormal development of connectivity may affect neuronal maturation and consequently the balance of excitation and inhibition in neuronal circuits, leading to their epileptogenic potential.