Vercellino Marco, Plano Federica, Votta Barbara, Mutani Roberto, Giordana Maria Teresa, Cavalla Paola
Department of Neuroscience, University of Turin, Turin, Italy.
J Neuropathol Exp Neurol. 2005 Dec;64(12):1101-7. doi: 10.1097/01.jnen.0000190067.20935.42.
The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurofilaments, synaptophysin, ubiquitin, and activated caspase-3. Neuronal density and optical density of synaptophysin staining were estimated in cortical lesions and compared with those observed in corresponding areas of normal (i.e. nondemyelinated) cortex in the same section. Demyelinating lesions were observed in the cerebral cortex, in the thalamus, basal ganglia, and in the hippocampus. The percentage of demyelinated cortex was remarkable in 2 cases of secondary progressive MS (48% and 25.5%, respectively). Neuronal density was significantly reduced in cortical lesions (18-23% reduction), if compared with adjacent normal cortex, in the 2 cases showing the higher extent of cortical demyelination; in the same cases, very rare apoptotic neurons expressing caspase-3 were observed in cortical lesions and not in adjacent normal cortex. No significant decrease in optical density of synaptophysin staining was observed in cortical lesions. Grey matter demyelination and neuronal loss could contribute to disability and cognitive dysfunctions in MS.
我们研究的目的是评估多发性硬化症（MS）中灰质脱髓鞘病变的程度和分布情况，同时探讨神经元丢失和突触丢失。选取了6例MS患者大脑和6例对照大脑的全冠状切片。对髓鞘碱性蛋白、神经丝、突触素、泛素和活化的半胱天冬酶-3进行免疫组织化学检测。估计皮质病变中神经元密度和突触素染色的光密度，并与同一切片中正常（即未脱髓鞘）皮质相应区域观察到的情况进行比较。在大脑皮质、丘脑、基底神经节和海马体中均观察到脱髓鞘病变。在2例继发进展型MS中，脱髓鞘皮质的百分比显著（分别为48%和25.5%）。在2例皮质脱髓鞘程度较高的病例中，与相邻正常皮质相比，皮质病变中的神经元密度显著降低（降低18 - 23%）；在相同病例中，在皮质病变中观察到极少量表达半胱天冬酶-3的凋亡神经元，而在相邻正常皮质中未观察到。在皮质病变中未观察到突触素染色光密度的显著降低。灰质脱髓鞘和神经元丢失可能导致MS患者的残疾和认知功能障碍。
