Background

The ratio between excitatory (glutamatergic) and inhibitory (GABAergic) inputs into maturing individual cortical neurons influences their epileptic potential. Structural factors during development that alter synaptic inputs can be demonstrated neuropathologically. Increased mitochondrial activity identifies neurons with excessive discharge rates.

Methods

This study focuses on the neuropathological examinaion of surgical resections for epilepsy and at autopsy, in fetuses, infants, and children, using immunocytochemical markers, and electron microscopy in selected cases. Polymicrogyria and Down syndrome are highlighted.

Results

Factors influencing afferent synaptic ratios include the following: (1) synaptic short-circuitry in fused molecular zones of adjacent gyri (polymicrogyria); (2) impaired development of dendritic spines decreasing excitation (Down syndrome); (3) extracellular keratan sulfate proteoglycan binding to somatic membranes but not dendritic spines may be focally diminished (cerebral atrophy, schizencephaly, lissencephaly, polymicrogyria) or augmented, ensheathing individual axons (holoprosencephaly), or acting as a barrier to axonal passage in the U-fiber layer. If keratan is diminished, glutamate receptors on the neuronal soma enable ectopic axosomatic excitatory synapses to form; (4) dysplastic, megalocytic neurons and balloon cells in mammalian target of rapamycin disorders; (5) satellitosis of glial cells displacing axosomatic synapses; (6) peri-neuronal inflammation (tuberous sclerosis) and heat-shock proteins.

Conclusions

Synaptic ratio of excitatory/inhibitory afferents is a major fundamental basis of epileptogenesis at the neuronal level. Neuropathology can demonstrate subcellular changes that help explain either epilepsy or lack of seizures in immature brains. Synaptic ratios in malformations influence postnatal epileptogenesis. Single neurons can be hypermetabolic and potentially epileptogenic.

中文翻译：

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多小脑回和唐氏综合症的兴奋性/抑制性突触比率有助于解释畸形的癫痫发生

背景

成熟的单个皮层神经元的兴奋性（谷氨酸能）和抑制性（GABAergic）输入之间的比率会影响它们的癫痫潜能。可以在神经病理学上证明发育过程中改变突触输入的结构因素。线粒体活性的增加可以识别出放电率过高的神经元。

方法

本研究侧重于在选定病例中使用免疫细胞化学标记物和电子显微镜对癫痫手术切除和尸检、胎儿、婴儿和儿童进行神经病理学检查。突出显示多小脑回和唐氏综合症。

结果

影响传入突触比率的因素包括：（1）相邻回旋（polymicrogyria）融合分子区的突触短路；(2) 树突棘发育受损，降低兴奋（唐氏综合症）；(3) 胞外硫酸角质素蛋白多糖与体细胞膜结合但不与树突棘结合可能会局部减少（脑萎缩、裂脑畸形、无脑回畸形、多小脑回）或增强、包裹单个轴突（前脑全裂），或充当 U 中轴突通道的屏障-纤维层。如果角蛋白减少，神经元胞体上的谷氨酸受体使异位轴体兴奋性突触形成；(4) 哺乳动物雷帕霉素靶点异常增生、巨细胞神经元和球囊细胞；(5) 取代轴体突触的神经胶质细胞的卫星化；

结论

兴奋性/抑制性传入神经的突触比率是神经元水平癫痫发生的主要基础。神经病理学可以证明亚细胞变化有助于解释未成熟大脑中的癫痫或癫痫发作的缺乏。畸形中的突触比率影响产后癫痫发生。单个神经元可能是高代谢和潜在致癫痫的。