title: Complement and blood-brain barrier integrity.
abstract: The blood-brain barrier (BBB) is structurally unique and regulates what is transported into and out of the brain, thereby maintaining brain homeostasis. In inflammatory settings the BBB becomes leaky, regulation of transport is lost and neuronal function goes awry. It is caused by a number of mediators such as complement activation products, processes and networks going haywire, the exact cellular and molecular mechanisms of which remain an enigma. Complement activation byproduct, C5a signaling through its G-protein coupled receptor C5aR1/CD88 increased BBB permeability in neuroinflammatory disease settings in vivo. Studies in brain endothelial cells in vitro demonstrated that the C5a/C5aR1 signaling occurred through the NF-κB pathway and altered miRNA in these cells. Inhibition or deletion of C5aR1 was protective in brain, both in vivo and in vitro revealing their potential as possible effective therapeutic targets. Although, this is a field where progress has been made, yet a lot remains to be done due to a number of limitations. This review will deal with the advances in the experimental models, technology and the underlying mechanisms causing the BBB pathology, with an emphasis on the complement proteins and their downstream mechanisms.
authors.affiliation: Department of Medicine, University at Buffalo, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Medicine, University at Buffalo, USA. Electronic address: jessyale@buffalo.edu.
authors.forename: Jessy John
authors.initials: JJ
authors.lastname: Alexander
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010539:Permeability
chemical_list: D003165:Complement System Proteins
keywords: Blood–brain barrier; Complement; Neurodegeneration