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Blood-Brain Barrier Transporters and Neuorinflammation: Partners in Neuroprotection and in Pathology


Makrides, V; Dolgodilina, Elena; Virgintino, D (2017). Blood-Brain Barrier Transporters and Neuorinflammation: Partners in Neuroprotection and in Pathology. In: Lyck, R; Enzmann, Gaby. The Blood Brain Barrier and Inflammation. Cham: Springer, 103-151.

Abstract

The blood–brain barrier (BBB) controls brain access of molecules and cells, communicates immune status to the central nervous system (CNS), and coordinates responses. Almost all solutes reach the brain from the blood through BBB transendothelial transporters that are often differentially localized on luminal and abluminal endothelial membranes. Therefore, BBB transporters crucially regulate CNS homeostasis and physiological responses to internal and external stimuli. Although the main functions of inflammatory processes are to remove the causes of the insult, to clear necrotic tissue, and to initiate tissue repair, these signals are often associated with further CNS damage in neuroinflammation. The BBB can aid adaptive responses; however, one hallmark of neuroinflammation is a breakdown of the tight endothelial barrier resulting in BBB opening, vascular leakage, and the loss of control over transendothelial transport. Thus, neuroinflammation often leads to pathological changes in CNS functions, such as those associated with the chronic age-related neuropathologies, Alzheimer’s disease and Parkinson’s disease, mechanical or physical insult and injury to the CNS (traumatic brain injury), infection, oncogenic diseases, and chronic autoimmune diseases, such as, multiple sclerosis and diabetes mellitus. Here, we review responses of selected ATP-binding cassette, solute carrier, receptor, and vesicular BBB endothelial transporters to neuroinflammatory mediators and diseases. Much emains to be learned concerning interactions of age, gender, genetics, microbiome, circadian cycle, diet, exercise, medication, etc., in neuroinflammatory processes. Crucially, in many regards, it is still unclear what tips the system from providing protective to effecting destructive responses.

Abstract

The blood–brain barrier (BBB) controls brain access of molecules and cells, communicates immune status to the central nervous system (CNS), and coordinates responses. Almost all solutes reach the brain from the blood through BBB transendothelial transporters that are often differentially localized on luminal and abluminal endothelial membranes. Therefore, BBB transporters crucially regulate CNS homeostasis and physiological responses to internal and external stimuli. Although the main functions of inflammatory processes are to remove the causes of the insult, to clear necrotic tissue, and to initiate tissue repair, these signals are often associated with further CNS damage in neuroinflammation. The BBB can aid adaptive responses; however, one hallmark of neuroinflammation is a breakdown of the tight endothelial barrier resulting in BBB opening, vascular leakage, and the loss of control over transendothelial transport. Thus, neuroinflammation often leads to pathological changes in CNS functions, such as those associated with the chronic age-related neuropathologies, Alzheimer’s disease and Parkinson’s disease, mechanical or physical insult and injury to the CNS (traumatic brain injury), infection, oncogenic diseases, and chronic autoimmune diseases, such as, multiple sclerosis and diabetes mellitus. Here, we review responses of selected ATP-binding cassette, solute carrier, receptor, and vesicular BBB endothelial transporters to neuroinflammatory mediators and diseases. Much emains to be learned concerning interactions of age, gender, genetics, microbiome, circadian cycle, diet, exercise, medication, etc., in neuroinflammatory processes. Crucially, in many regards, it is still unclear what tips the system from providing protective to effecting destructive responses.

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Additional indexing

Item Type:Book Section, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2017
Deposited On:11 Jan 2018 11:26
Last Modified:19 Feb 2018 08:42
Publisher:Springer
ISBN:978-3-319-45512-9
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/978-3-319-45514-3

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