title: Albumin and multiple sclerosis.
abstract: Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA. slevine@kumc.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: LeVine
mesh_terms: D000418:Albumins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000378:metabolism; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism
chemical_list: D000418:Albumins; D016207:Cytokines; D018698:Glutamic Acid
keywords: Albumin; Albumin quotient; Blood–brain barrier; Cerebrospinal fluid; Experimental autoimmune encephalomyelitis; Macrophages; Multiple sclerosis; Reactive nitrogen species; Reactive oxygen species