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Minimal penetration of lipopolysaccharide across the murine blood–brain barrier
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LPS given peripherally or into the brain induces a neuroinflammatory response. How peripheral LPS induces its effects on brain is not clear, but one mechanism is that LPS crosses the blood-brain barrier (BBB). Alternatively, LPS acts outside the BBB by stimulating afferent nerves, acting at circumventricular organs, and altering BBB permeabilities and functions. Here, we labeled LPS with radioactive iodine (I-LPS) and coinjected it with radioactively labeled albumin (I-Alb) which acted as a vascular space marker. Measurable amounts of I-LPS associated with the BBB, most reversibly bound to brain endothelia. Brain endothelia also sequestered small amounts of I-LPS and about 0.025% of an intravenously injected dose of I-LPS crossed the BBB to enter the CNS. Disruption of the BBB with repeated injections of LPS did not enhance I-LPS uptake. Based on dose-response curves in the literature of the amounts of LPS needed to stimulate brain neuroimmune events, it is unlikely that enough peripherally administered LPS enters the CNS to invoke those events except possibly at the highest doses used and for the most sensitive brain functions. I-LPS injected into the lateral ventricle of the brain entered the circulation with the reabsorption of cerebrospinal fluid (bulk flow) as previously described. In conclusion, brain uptake of circulating I-LPS is so low that most effects of peripherally administered LPS are likely mediated through LPS receptors located outside the BBB.
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“Low and medium doses of endotoxin do not change blood-brain barrier permeability and only minimally enter the brain [52], suggesting that peripheral LPS may induce brain inflammation indirectly by (i) LPS activation of peripheral nerves acting centrally; (ii) LPS activation of the blood-brain barrier, which then releases cytokines within the brain, or recruiting immune cells into the brain; or (ii”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [52]
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Metadata
- Authors
- Banks, W. A., & Robinson, S. M.
- Affiliations
- St. Louis VA Medical Center (US)
- Corresponding author
- Banks, William A.
- ORCID
- Banks, William A.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 24
- Issue
- 1
- Pages
- 102-109
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2789209
- OpenAlex
- W2065678433
- Cited by
- 356
- References
- 45
- Citations by year
- 2026: 19 · 2025: 15 · 2024: 34 · 2023: 36 · 2022: 24 · 2021: 35 · 2020: 28 · 2019: 19 · 2018: 28 · 2017: 20 · 2016: 27 · 2015: 11 · 2014: 18 · 2013: 13 · 2012: 14
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG029839, AG029839)
- National Institute of Neurological Disorders and Stroke (NS05047)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- lipopolysaccharide, blood-brain barrier, blood-brain barrier permeability, brain endothelium, neuroinflammation, circumventricular organs, afferent nerves, LPS receptor, lateral ventricle injection
- MeSH terms
- Octanols, Algorithms, Animals, Blood-Brain Barrier, Capillaries, Cerebrovascular Circulation, Dose-Response Relationship, Drug, Immunity, Innate, Injections, Intravenous, Injections, Intraventricular, Lipopolysaccharides, Male, Solubility, Salmonella enterica, Mice
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