Fibrin mechanisms and functions in nervous system pathology.
In brain physiology, cerebrovascular interactions regulate both, vascular functions, such as blood vessel branching and endothelial cell homeostasis, as well as neuronal functions, such as local synaptic activity and adult neurogenesis. In brain pathology, including stroke, HIV encephalitis, Alzheimer Disease, multiple sclerosis, bacterial meningitis, and glioblastomas, rupture of the vasculature allows the entry of blood proteins into the brain with subsequent edema formation and neuronal damage. Fibrin is a blood-derived protein that is not produced by cells of the nervous system, but accumulates only after disease associated with vasculature rupture. This review presents evidence from human disease and animal models that highlight the role of fibrin in nervous system pathology. Our review presents novel experimental data that extend the role of fibrin, from that of a blood-clotting protein in cerebrovascular pathologies, to a component of the perivascular extracellular matrix that regulates inflammatory and regenerative cellular responses in neurodegenerative diseases.
Adams
Ryan A
RA
Department of Pharmacology, University of California-San Diego, La Jolla, CA 92093-0636, USA.
Passino
Melissa
M
Sachs
Benjamin D
BD
Nuriel
Tal
T
Akassoglou
Katerina
K
D000595:Amino Acid Sequence; D000721:Ancrod / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009420:Nervous System / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D005343:Fibrinolytic Agents; D005337:Fibrin; D005340:Fibrinogen; D000721:Ancrod