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梗阻性脑积水脑脊液中 AQP1 的过表达及其在 Chiari 畸形 II 型脉络丛中的极性反转。

AQP1 Overexpression in the CSF of Obstructive Hydrocephalus and Inversion of Its Polarity in the Choroid Plexus of a Chiari Malformation Type II Case.

机构信息

Department of Neurological Surgery, Washington University, School of Medicine and the St. Louis Children's Hospital, St. Louis, Missouri.

Instituto de Investigación y Ciencias, Puerto del Rosario, Fuerteventura.

出版信息

J Neuropathol Exp Neurol. 2019 Jul 1;78(7):641-647. doi: 10.1093/jnen/nlz033.

Abstract

The choroid plexus (ChP) is involved in the production of cerebrospinal fluid (CSF) and is intimately related to CSF physiopathology. Aquaporin-1 (AQP1) is the water channel directly implicated in CSF production and a potential therapeutic target in the management of CSF circulation disorders. Pathologies that present ventriculomegaly are associated with defective CSF turnover and AQPs are involved in both the production and reabsorption of CSF. This work examines the levels of AQP1 and its dynamics in ventriculomegaly conditions such as congenital hydrocephalus (communicating and obstructive) or type II lissencephaly versus control. We specifically address the expression of AQP1 in the CSF of 16 term-pregnancy infants where it was found to be significantly increased in obstructive cases when compared with communicating hydrocephalus or control patients. We also defined histologically the expression of AQP1 in the ChP from 6 nonsurvival preterm-pregnancy infants ranging ages between 20 and 25 gestational weeks in which AQP1 was mainly expressed at the apical pole of the ChP epithelium (ChPE) in control and lissencephalic patients. AQP1 expression from the Chiari malformation case showed an inverted polarity being expressed in the basal pole of the ChPE colocalizing with the glucose transporter 1 where this transporter is naturally located.

摘要

脉络丛(ChP)参与脑脊液(CSF)的产生,与 CSF 病理生理学密切相关。水通道蛋白-1(AQP1)是直接参与 CSF 产生的水通道,也是 CSF 循环障碍管理的潜在治疗靶点。出现脑室扩大的病理与 CSF 周转率缺陷有关,而 AQPs 参与 CSF 的产生和再吸收。本研究检查了在先天性脑积水(交通性和梗阻性)或 II 型无脑回畸形等脑室扩大情况下 AQP1 的水平及其动态,与对照组相比,发现梗阻性病例中 AQP1 的表达显著增加。我们还在组织学上定义了 6 例非存活早产儿脉络丛中的 AQP1 表达,这些早产儿的胎龄在 20 至 25 周之间,在对照组和无脑回畸形患者中,AQP1 主要在脉络丛上皮(ChPE)的顶端表达。Chiari 畸形病例的 AQP1 表达呈倒置极性,在 ChPE 的基底部表达,与葡萄糖转运蛋白 1 共定位,而该转运蛋白自然位于该部位。

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