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脑膜和脉络丛细胞--中枢神经系统疾病的新药物靶点。

Meningeal and choroid plexus cells--novel drug targets for CNS disorders.

机构信息

Department of Pharmacology and Centre for Brain Research, The University of Auckland, Auckland, New Zealand.

出版信息

Brain Res. 2013 Mar 21;1501:32-55. doi: 10.1016/j.brainres.2013.01.013. Epub 2013 Jan 14.

DOI:10.1016/j.brainres.2013.01.013
PMID:23328079
Abstract

The meninges and choroid plexus perform many functions in the developing and adult human central nervous system (CNS) and are composed of a number of different cell types. In this article I focus on meningeal and choroid plexus cells as targets for the development of drugs to treat a range of traumatic, ischemic and chronic brain disorders. Meningeal cells are involved in cortical development (and their dysfunction may be involved in cortical dysplasia), fibrotic scar formation after traumatic brain injuries (TBI), brain inflammation following infections, and neurodegenerative disorders such as Multiple Sclerosis (MS) and Alzheimer's disease (AD) and other brain disorders. The choroid plexus regulates the composition of the cerebrospinal fluid (CSF) as well as brain entry of inflammatory cells under basal conditions and after injuries. The meninges and choroid plexus also link peripheral inflammation (occurring in the metabolic syndrome and after infections) to CNS inflammation which may contribute to the development and progression of a range of CNS neurological and psychiatric disorders. They respond to cytokines generated systemically and secrete cytokines and chemokines that have powerful effects on the brain. The meninges may also provide a stem cell niche in the adult brain which could be harnessed for brain repair. Targeting meningeal and choroid plexus cells with therapeutic agents may provide novel therapies for a range of human brain disorders.

摘要

脑膜和脉络丛在人类中枢神经系统(CNS)的发育和成年中发挥许多功能,由许多不同的细胞类型组成。在本文中,我专注于脑膜和脉络丛细胞作为开发药物治疗一系列创伤性、缺血性和慢性脑疾病的靶点。脑膜细胞参与皮质发育(其功能障碍可能与皮质发育不良有关)、创伤性脑损伤(TBI)后的纤维瘢痕形成、感染后的脑炎症以及多发性硬化症(MS)和阿尔茨海默病(AD)等神经退行性疾病以及其他脑疾病。脉络丛调节脑脊液(CSF)的组成以及在基础条件下和受伤后的炎症细胞进入大脑的情况。脑膜和脉络丛还将外周炎症(发生在代谢综合征和感染后)与中枢神经系统炎症联系起来,这可能导致一系列中枢神经系统神经和精神疾病的发展和进展。它们对全身产生的细胞因子作出反应,并分泌细胞因子和趋化因子,对大脑产生强大的影响。脑膜在成人大脑中也可能提供一个干细胞龛,可以用于大脑修复。针对脑膜和脉络丛细胞的治疗剂可能为一系列人类脑疾病提供新的治疗方法。

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