Blümcke I, Beck H, Suter B, Hoffmann D, Födisch H J, Wolf H K, Schramm J, Elger C E, Wiestler O D
Department of Neuropathology, University of Bonn Medical Center, Germany.
Acta Neuropathol. 1999 Jan;97(1):31-9. doi: 10.1007/s004010050952.
Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS). Previous data demonstrate an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells are transiently expressed in the murine developing hippocampus and are critically involved in neuronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally oriented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal formation have been visualized by antibodies against the calcium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During ontogeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hippocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher levels of CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a considerable number of TLE patients with AHS display signs of impaired hippocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It remains to be elucidated, how these changes contribute to the pathogenesis of TLE.
大量研究表明，诸如幼儿期热性惊厥等初始促发损伤（IPI）可能在颞叶癫痫（TLE）和海马硬化（AHS）的发病机制中起关键作用。先前的数据表明，海马亚区分子层中水平方向排列的神经元数量增加，这些神经元对钙视网膜蛋白（CR-ir）具有免疫反应性，类似于 Cajal-Retzius 样细胞。Cajal-Retzius 细胞在小鼠发育中的海马中短暂表达，并在神经元模式形成中起关键作用。在此，我们研究了水平方向排列的钙视网膜蛋白免疫反应性神经元的分布与患有 AHS 的 TLE 患者临床病史之间的潜在关系。通过针对钙结合蛋白钙视网膜蛋白和钙结合蛋白 D-28k 的抗体，观察到海马结构分子层中水平方向排列的神经元。将 27 例患有 AHS 的癫痫患者的细胞计数与发育中和成年正常人类海马的尸检标本（n = 26）进行比较。在个体发育过程中，CR-ir 细胞在 CA1 和齿状回分子层（CA1-ML，DG-ML）中显示出明显的围产期峰值，随后在出生后逐渐下降。在 4 岁前发病的患有 AHS 的 TLE 患者的海马标本中，CA1-ML（P = 0.05）和 DG-ML（P < 0.05）中的 CR-ir 神经元水平显著高于无促发癫痫发作或早期病史平稳的 AHS 患者。然而，与尸检获得的成年对照组相比，所有三组的 CR-ir 神经元水平都更高（P < 0.01）。此外，与对照组中可见的浅颗粒细胞层内 CR-ir 纤维的局限分布相比，AHS 标本在整个 DG-ML 中显示出 CR-ir 神经毡染色增加。这些发现表明，相当数量的患有 AHS 的 TLE 患者表现出海马成熟和电路形成受损的迹象，如 Cajal-Retzius 样细胞数量增加所示。这些变化如何导致 TLE 的发病机制仍有待阐明。
