Calbindin D28K expression in relation to granule cell dispersion, mossy fibre sprouting and memory impairment in hippocampal sclerosis: A surgical and post mortem series

Calbindin D28K expression in relation to granule cell dispersion, mossy fibre sprouting and memory impairment in hippocampal sclerosis: A surgical and post mortem series
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DOI:
10.1016/j.eplepsyres.2011.08.011
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发表时间:
2012-01-01
期刊:
影响因子:
2.2
通讯作者:
Thom, M.
Thom, M.
中科院分区:
医学4区
文献类型:
--
作者:
Martinian, L.;Catarino, C. B.;Thom, M.

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齿状回的重组,包括颗粒细胞弥散(GCD)和苔藓纤维发芽,典型地伴随着颞叶癫痫的海马硬化(HS)。钙结合蛋白(CB)在颗粒细胞中的表达在婴儿期增加,影响颗粒细胞的兴奋性、对兴奋性毒性的易感性以及在记忆中的重要生理功能。我们的目的是研究CB模式与齿状回重组、癫痫病史和记忆功能的关系。除了3例尸检外,我们还检查了45例手术病例和11例尸检病例。在手术病例中,测量CB的表达,以及GCD和苔藓纤维发芽的程度。在尸检病例中,CB的表达与海马吻侧尾轴线上HS的模式有关,并与PM对照组进行比较。第1组(40%),颗粒细胞以CB阳性为主,基底细胞阴性,呈类似发育模式。第2组(47%)CB表达正常,第3组(13%)CB主要缺失于颗粒细胞。这些模式与GCD、苔藓纤维发芽和HS模式相关。第1组与癫痫的早期发作有关,但不能独立预测结果。在尸检病例中,改变的CB表达偏侧于HS侧,尽管有些患者癫痫缓解,但仍持续存在。CB的表达与记忆功能之间没有明显的相关性。CB在HS中的表达模式可能表明发育不成熟,并与HS中GCD和苔藓纤维发芽的程度有关。CB丢失在癫痫发生和对记忆的影响方面的功能意义仍不确定。(C)2011爱思唯尔B.V.保留所有权利。
Reorganisation of the dentate gyrus, including granule cell dispersion (GCD) and mossy fibre sprouting, typically accompany hippocampal sclerosis (HS) in temporal lobe epilepsy. Calbindin (CB) expression in granule cells increases during infancy, influences granule cell excitability, vulnerability to excitotoxicity in addition to important physiological functions in memory. Our aim was to study CB patterns in relation to dentate gyrus re-organisation, epilepsy history and memory function.Forty-five surgical cases and 11 post mortems were examined from patients with drug-resistant epilepsy in addition to three post mortem controls. In the surgical cases, CB expression, and the degree of GCD and mossy fibre sprouting were measured. In post mortem cases, CB expression was assessed in relation to the pattern of HS along the rostral caudal axis of the hippocampus, and compared to PM controls.Three patterns were identified. In Group 1 (40%), the most dispersed granule cells were CB-positive and basal cells negative imitating developmental patterns. In Group 2 (47%), normal CB expression was retained and in Group 3(13%), CB was predominantly lost in granule cells. These patterns correlated with GCD, the presence of mossy fibre sprouting and the pattern of HS. Group 1 was associated with early onset of seizures but not independently predictive of outcome. In post mortem cases, altered CB expression lateralised to the side of HS and persisted despite seizure remission in some patients. No significant correlation between CB expression and memory function was identified.CB expression patterns in HS may indicate developmental dysmaturation and are associated with the extent of GCD and mossy fibre sprouting in HS. The functional significance of CB loss, in terms of epileptogenesis and effects on memory, remain uncertain. (C) 2011 Elsevier B.V. All rights reserved.