Dataset Information

Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders.

ABSTRACT: The blood-brain barrier (BBB) is a dynamic but solid shield in the cerebral microvascular system. It plays a pivotal role in maintaining central nervous system (CNS) homeostasis by regulating the exchange of materials between the circulation and the brain and protects the neural tissue from neurotoxic components as well as pathogens. Here, we discuss the development of the BBB in physiological conditions and then focus on the role of the BBB in cerebrovascular disease, including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Finally, we summarize recent advancements in the development of therapies targeting the BBB and outline future directions and outstanding questions in the field. We propose that BBB dysfunction not only results from, but is causal in the pathogenesis of neurological disorders; the BBB is more a contributor to the disruption of CNS homeostasis than a victim in neurological disorders.

SUBMITTER: Xiao M

PROVIDER: S-EPMC7438939 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders.

Xiao Minjia M Xiao Zhi Jie ZJ Yang Binbin B Lan Ziwei Z Fang Fang F

Frontiers in neuroscience 20200806

The blood-brain barrier (BBB) is a dynamic but solid shield in the cerebral microvascular system. It plays a pivotal role in maintaining central nervous system (CNS) homeostasis by regulating the exchange of materials between the circulation and the brain and protects the neural tissue from neurotoxic components as well as pathogens. Here, we discuss the development of the BBB in physiological conditions and then focus on the role of the BBB in cerebrovascular disease, including acute ischemic s ...[more]

PMID: 32903669

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Project description:The blood-brain barrier (BBB) allows the brain to selectively import nutrients and energy critical to neuronal function while simultaneously excluding neurotoxic substances from the peripheral circulation. In contrast to the highly permeable vasculature present in most organs that reside outside of the central nervous system (CNS), the BBB exhibits a high transendothelial electrical resistance (TEER) along with a low rate of transcytosis and greatly restricted paracellular permeability. The property of low paracellular permeability is controlled by tight junction (TJ) protein complexes that seal the paracellular route between apposing brain microvascular endothelial cells. Although tight junction protein complexes are principal contributors to physical barrier properties, they are not static in nature. Rather, tight junction protein complexes are highly dynamic structures, where expression and/or localization of individual constituent proteins can be modified in response to pathophysiological stressors. These stressors induce modifications to tight junction protein complexes that involve de novo synthesis of new protein or discrete trafficking mechanisms. Such responsiveness of BBB tight junctions to diseases indicates that these protein complexes are critical for maintenance of CNS homeostasis. In fulfillment of this vital role, BBB tight junctions are also a major obstacle to therapeutic drug delivery to the brain. There is an opportunity to overcome this substantial obstacle and optimize neuropharmacology via acquisition of a detailed understanding of BBB tight junction structure, function, and regulation. In this review, we discuss physiological characteristics of tight junction protein complexes and how these properties regulate delivery of therapeutics to the CNS for treatment of neurological diseases. Specifically, we will discuss modulation of tight junction structure, function, and regulation both in the context of disease states and in the setting of pharmacotherapy. In particular, we will highlight how these properties can be potentially manipulated at the molecular level to increase CNS drug levels via paracellular transport to the brain.

Dataset Information

Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders.

Publications

Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders.

Similar Datasets

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