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脑积水时的神经元损伤及其在实验性脑积水中通过分流术的恢复:一项涉及神经丝免疫染色法的研究。

Neuronal damage in hydrocephalus and its restoration by shunt insertion in experimental hydrocephalus: a study involving the neurofilament-immunostaining method.

作者信息

Aoyama Yuichi, Kinoshita Yoshimasa, Yokota Akira, Hamada Tetsuo

机构信息

Departments of Neurosurgery and Surgical Pathology, University of Occupational and Environmental Health, Kitakyushu, Japan.

出版信息

J Neurosurg. 2006 May;104(5 Suppl):332-9. doi: 10.3171/ped.2006.104.5.332.

Abstract

OBJECT

The morphological and functional impairments of neurons and their connections caused by hydrocephalus, and their restoration by ventricular shunt placement were investigated in experimental hydrocephalus by the immunostaining of neurofilaments, which constitute the major component of the neuronal cytoskeleton.

METHODS

Progressive hydrocephalus was induced in 15 young mongrel dogs 1 to 2 months of age, 3 to 4 weeks after cisternal injection of kaolin. The dogs were divided into three groups of five animals each, a "preshunt," "post-shunt," and "nonshunt" group, depending on whether the hydrocephalic animals underwent a procedure to insert a ventriculoperitoneal shunt. Neurofilament, glial fibrillary acid protein (GFAP), and synaptophysin immunostaining were performed using samples of brain tissue from each hydrocephalic group and a fourth "control" group (five animals). In the cortex, morphological deformation and heterogeneous neurofilament immunoreactivity of the apical dendrites became pronounced in accordance with the progression of hydrocephalus (from the preshunt to the nonshunt group), and these changes remained after shunt insertion (postshunt group). In the periventricular white matter, swollen and fragmented axons increased in number along with hydrocephalic progression and were incompletely repaired by ventricular shunt placement. The GFAP-positive astrocytes observed around repaired axons in the postshunt group were seen more prominently than in the untreated hydrocephalic groups. In the internal capsule, fairly good recovery from axonal damage caused by the hydrocephalic condition was achieved by insertion of a ventricular shunt, compared with that seen in the periventricular white matter.

CONCLUSIONS

Cytoskeletal damage of neurons in hydrocephalus and its incomplete restoration by shunt placement were most significant in the periventricular white matter. This finding may account for the impaired cognitive function seen in children who have shunts and an apparently reconstituted cerebral mantle; therefore, neuronal protection in the early hydrocephalic state should be considered.

摘要

目的

通过对构成神经元细胞骨架主要成分的神经丝进行免疫染色,在实验性脑积水模型中研究脑积水导致的神经元及其连接的形态和功能损伤,以及脑室分流术对其的修复作用。

方法

在15只1至2月龄的年轻杂种犬中,于小脑延髓池注射高岭土3至4周后诱导进行性脑积水。根据脑积水动物是否接受脑室腹腔分流术的插入操作,将这些犬分为三组,每组五只动物,分别为“分流前”、“分流后”和“未分流”组。使用来自每个脑积水组和第四个“对照组”(五只动物)的脑组织样本进行神经丝、胶质纤维酸性蛋白(GFAP)和突触素免疫染色。在皮质中,随着脑积水的进展(从分流前组到未分流组),顶端树突的形态变形和神经丝免疫反应性异质性变得明显,并且这些变化在分流插入后(分流后组)仍然存在。在脑室周围白质中,随着脑积水进展,肿胀和断裂的轴突数量增加,脑室分流术未能完全修复这些损伤。与未治疗的脑积水组相比,分流后组中在修复轴突周围观察到的GFAP阳性星形胶质细胞更为明显。在内囊中,与脑室周围白质相比,通过插入脑室分流术可使脑积水引起的轴突损伤得到较好的恢复。

结论

脑积水时神经元的细胞骨架损伤及其通过分流术的不完全修复在脑室周围白质中最为显著。这一发现可能解释了接受分流术且脑皮质外观已恢复的儿童出现认知功能受损的原因;因此,应考虑在早期脑积水状态下对神经元进行保护。

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