Development of Choroid Plexus and the Blood-CSF Barrier

脉络丛和血脑脊液屏障的发育

• 批准号: 7140269
• 负责人: Angeliki Louvi
• 金额: $ 18.46万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140269
• 关键词: actin binding protein; blood brain barrier; chick embryo; choroid plexus; developmental neurobiology; growth /development; laboratory mouse; meninges; mesenchyme; neurogenesis; neuronal guidance; technology /technique development; tissue /cell culture

DESCRIPTION (provided by applicant): Blood-tissue barriers protect the central nervous system and represent the major interfaces between the central nervous system and peripheral circulation. Damage to the barriers leads to long-term neurological toxicity in the development of many neurological diseases. Barriers are found in the brain endothelium, the choroid plexus epithelium, and the arachnoid epithelium. Drug exposure to the CNS is partially dependent on the physical barrier presented by the blood-brain and blood-CSF barrier and the affinity of the substrate for specific transport systems located at both of these interfaces. The choroid plexus epithelium, together with the arachnoid epithelium and the circumventricular organs collectively constitute the blood-CSF barrier. The choroid plexus is involved in the production and secretion of CSF. Our understanding of choroid plexus developmental biology is extremely limited. The proposed studies aim at exploring the molecular and cellular mechanisms underlying the formation of the choroid plexus. More specifically, using a combination of molecular, cellular and embryological approaches, morphogenesis and maturation of the choroid plexus and the mechanisms that guide its formation as well as the establishment of its barrier functions will be addressed in the context of the developing animal and in cell culture-based assays. Our general aim is to provide a comprehensive characterization of the choroid plexus, the central element of the blood-CSF barrier and an important, yet overlooked structure in the brain, 1 that may be potentially explored as a target for drug and gene delivery strategies for the treatment of neurological diseases.

描述（由申请人提供）：血液组织屏障保护中枢神经系统，代表中枢神经系统和外周循环之间的主要界面。对屏障的破坏导致许多神经系统疾病发展中的长期神经毒性。在脑内皮、脉络丛上皮和蛛网膜上皮中发现屏障。药物暴露于CNS部分取决于血脑屏障和血CSF屏障的物理屏障以及底物对位于这两个界面的特定转运系统的亲和力。脉络丛上皮与蛛网膜上皮和室周器官共同构成血-CSF屏障。脉络丛参与CSF的产生和分泌。我们对脉络丛发育生物学的理解是非常有限的。这些研究旨在探索脉络丛形成的分子和细胞机制。更具体地说，使用分子，细胞和胚胎学的方法，形态发生和脉络丛的成熟和机制，指导其形成以及建立其屏障功能的组合将在发展中的动物的背景下，并在细胞培养为基础的测定。我们的总体目标是提供脉络丛的全面表征，脉络丛是血液-CSF屏障的中心要素，也是大脑中一个重要但被忽视的结构，1它可能被探索为治疗神经系统疾病的药物和基因递送策略的靶点。