Andrioli A, Alonso-Nanclares L, Arellano J I, DeFelipe J
Instituto Cajal (CSIC), Avda Dr Arce 37, 28002 Madrid, Spain.
Neuroscience. 2007 Oct 12;149(1):131-43. doi: 10.1016/j.neuroscience.2007.07.029. Epub 2007 Jul 25.
Hippocampal sclerosis is the most frequent pathology encountered in mesial temporal structures resected from patients with intractable temporal lobe epilepsy and it mainly involves hippocampal neuronal loss and gliosis. These alterations are accompanied by changes in the expression of a variety of molecules in the surviving neurons, as well as axonal reorganization in both excitatory and inhibitory circuits. The alteration of a subpopulation of GABAergic interneurons that expresses the calcium binding protein parvalbumin (PV) is thought to be a key factor in the epileptogenic process. We investigated the distribution and density of parvalbumin-immunoreactive (PV-ir) neurons in surgically resected hippocampal tissue from epileptic patients with and without sclerosis. Using quantitative stereological methods, we show for the first time that there is no correlation between total neuronal loss and PV-ir neuronal loss in any of the hippocampal fields. We also observed higher values of the total neuronal density in the sclerotic subiculum, which is accompanied by a lower density of PV-ir when compared with non-sclerotic epileptic and autopsy hippocampi. These findings suggest that, the apparently normal subiculum from sclerotic patients also shows unexpected changes in the density and proportion of PV-ir neurons.
海马硬化是难治性颞叶癫痫患者颞叶内侧结构切除术中最常见的病理表现,主要涉及海马神经元丢失和胶质增生。这些改变伴随着存活神经元中多种分子表达的变化,以及兴奋和抑制性回路中的轴突重组。表达钙结合蛋白小白蛋白(PV)的γ-氨基丁酸能中间神经元亚群的改变被认为是致痫过程中的关键因素。我们研究了有硬化和无硬化的癫痫患者手术切除的海马组织中PV免疫反应性(PV-ir)神经元的分布和密度。使用定量立体学方法,我们首次表明,在任何海马区域,总神经元丢失与PV-ir神经元丢失之间均无相关性。我们还观察到硬化海马下托的总神经元密度较高,与非硬化癫痫患者和尸检海马相比,PV-ir密度较低。这些发现表明,硬化患者看似正常的海马下托在PV-ir神经元的密度和比例上也显示出意外的变化。