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Cited by 105Multiple Sclerosis Research StudiesBarrier Structure and Function StudiesExtracellular vesicles in disease

Albumin and multiple sclerosis

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LeVine, Steven M.·2016·BMC Neurology
DOI 10.1186/s12883-016-0564-9PMC PMC4828783
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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.

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  • Brain macrophages, microglia, astrocytes, neurons, and NG2-positive cells can take up albumin.

    “Given that brain macrophages, microglia, astrocytes, neurons, and neuronglial antigen 2-positive cells can take up albumin (76, 286, 355)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [355]

    The Review section on BBB damage says albumin is taken up by subarachnoidal macrophages, astrocytes, microglia, and neurons. The passages found do not address uptake by NG2-positive cells, so that part of the attributed claim is unsupported by our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In multiple sclerosis patients at different stages of the disease, elevated Qalb values, increased MMP-9 activity in CSF and serum, and increased CSF leukocyte count have been shown, all indicative of blood-brain barrier breakdown.

    “Elevated Qalb values (355), increased MMP-9 activity in CSF and serum (122, 168), and increased CSF leukocyte count (122), all indicative of BBB breakdown, have been shown in MS patients at different stages of the disease.”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [355]

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Cited by

Sorted by citations

Authors
LeVine, S. M.
Affiliations
University of Kansas Medical Center (US)
Corresponding author
LeVine, Steven M.
ORCID
LeVine, Steven M.
Venue
BMC Neurology
Publisher
Springer Science and Business Media LLC
Published
2016-04-12
Volume
16
Issue
1
Pages
47-47
ISSN
1471-2377 (ISSN-L)
DOI
10.1186/s12883-016-0564-9
PMC
PMC4828783
OpenAlex
W2338740106
Cited by
105
References
197
Citations by year
2026: 9 · 2025: 3 · 2024: 19 · 2023: 8 · 2022: 16 · 2021: 12 · 2020: 15 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 4
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KU ScholarWorks (The University of Kansas) (submittedVersion, cc-by)
Funders
  • University of Kansas Medical Center (Intramural funds)
  • The One University Open Access Author Fund at The University of Kansas
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
albumin, multiple sclerosis, blood-brain barrier disruption, blood-CSF barrier dysfunction, albumin quotient, demyelination, reactive oxygen species, reactive nitrogen species, inflammatory cytokines, glutamate excitotoxicity, macrophages, microglia, cerebrospinal fluid albumin
MeSH terms
Albumins, Blood-Brain Barrier, Humans, Multiple Sclerosis, Neurons, Cytokines, Microglia, Glutamic Acid

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