Martinian L, Boer K, Middeldorp J, Hol E M, Sisodiya S M, Squier W, Aronica E, Thom M
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College, London, UK.
Neuropathol Appl Neurobiol. 2009 Aug;35(4):394-405. doi: 10.1111/j.1365-2990.2009.00996.x.
Glial fibrillary acidic protein (GFAP)-delta is a novel isoform that differs in its C-terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological conditions causing reactive gliosis. GFAP-delta is speculated to have roles in regulation of astrocyte size and motility and a subpopulation of GFAP-delta-positive glia may be multipotent stem cells. The aim of this study was to investigate its expression in common causes of lesion-related refractory epilepsy.
Hippocampal sclerosis (HS), focal cortical dysplasia (FCD) type IIB, cortical tuberous sclerosis (TSC) lesions, gangliogliomas, grey matter heterotopias and hemimegalencephaly from a wide age range of patients using both surgical and post mortem tissue specimens were studied.
GFAP-delta expression was observed in CA4 and CA1 astrocytes in HS with less frequent labelling in the granule cell layer, even where granule cell dispersion was present. No significant labelling was noted in the subiculum in HS cases or in any subfields in non-HS epilepsy cases. Balloon cells in FCDIIB and hemimegalencephaly, giant cells in TSC and the astrocytic component of gangliogliomas showed immunoreactivity, colocalizing with conventional GFAP. No neuronal expression for GFAP-delta was seen in any of the pathologies. Quantitative analysis in 10 FCDIIB and five TSC cases revealed greater numbers of GFAP-delta-positive balloon cells than conventional GFAP. There was no GFAP-delta expression within nodular heterotopia.
GFAP-delta expression patterns in HS overall appears to mirror regional reactive gliosis. It is a useful marker for the demonstration of balloon cells in FCD and TSC, which may be relevant to their abnormal size and localization. The lack of GFAP-delta within heterotopia supports their composition from cells destined for deeper cortical layers.
胶质纤维酸性蛋白（GFAP）-δ是一种新型异构体，其C末端序列与其他GFAP异构体不同。先前的研究表明，其表达局限于软脑膜层、脑室下区和颗粒下区星形胶质细胞，在导致反应性胶质增生的病理条件下不存在。推测GFAP-δ在调节星形胶质细胞大小和运动性方面发挥作用，并且GFAP-δ阳性神经胶质细胞亚群可能是多能干细胞。本研究的目的是调查其在与病变相关的难治性癫痫常见病因中的表达情况。
使用手术和尸检组织标本，对广泛年龄范围患者的海马硬化（HS）、IIB型局灶性皮质发育不良（FCD）、皮质结节性硬化症（TSC）病变、神经节胶质瘤、灰质异位症和半侧巨脑症进行研究。
在HS的CA4和CA1星形胶质细胞中观察到GFAP-δ表达，在颗粒细胞层中标记频率较低，即使存在颗粒细胞分散的情况。在HS病例的海马下托或非HS癫痫病例的任何亚区中均未观察到明显标记。FCDIIB和半侧巨脑症中的气球样细胞、TSC中的巨细胞以及神经节胶质瘤的星形胶质细胞成分显示免疫反应性，与传统GFAP共定位。在任何病理情况下均未观察到GFAP-δ的神经元表达。对10例FCDIIB和5例TSC病例的定量分析显示，GFAP-δ阳性气球样细胞数量多于传统GFAP。结节性异位症内未观察到GFAP-δ表达。
HS中GFAP-δ的表达模式总体上似乎反映了区域反应性胶质增生。它是用于显示FCD和TSC中气球样细胞的有用标志物，这可能与其异常大小和定位有关。异位症内缺乏GFAP-δ支持其由注定位于更深皮质层的细胞组成。
