Bothwell S, Meredith G E, Phillips J, Staunton H, Doherty C, Grigorenko E, Glazier S, Deadwyler S A, O'Donovan C A, Farrell M
Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland.
J Neurosci. 2001 Jul 1;21(13):4789-800. doi: 10.1523/JNEUROSCI.21-13-04789.2001.
The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.
新皮质受累于颞叶癫痫（TLE）的潜在原因仍是一个基本且未得到解答的问题。磁共振成像显示颞叶体积显著减小，有人提出由于神经元丢失，新皮质回路在功能上受到干扰。本研究使用基于设计的体视学方法来估计布罗德曼38区的体积和细胞数量，该区域在前颞叶切除术中常被切除。研究对象为有或无海马硬化（HS）的患者的新皮质。结果得出了一个惊人的发现，即TLE患者新皮质灰质有明显萎缩，但神经元没有丢失。与对照组相比，TLE标本中的神经元也明显更大，树突分支显得更稀疏，且棘突密度显著降低。因此，我们在TLE患者中发现的神经元密度增加是由于大神经元所占体积比正常脑小得多。深层白质中的神经元大小也增加，但与其他报告不同的是，其数量或密度没有显著升高。神经元肥大对有HS和无HS的脑的影响相似。因此，神经毡及其相关成分的减少似乎是TLE的一个主要特征，并非继发于细胞丢失。在灰质和白质中，神经元肥大意味着更多的核周表面积暴露用于突触接触，并成为这种疾病的一个标志。
