Early detection of liposome brain localization in rat experimental allergic encephalomyelitis.
Abstract
Blood-brain barrier (BBB) permeability increases prior to the development of clinical signs in early-stage multiple sclerosis (MS). Detection of subtle changes would thus be helpful for diagnostic purposes and rapid therapeutic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particular BBB-permeability characteristics, and since we have previously shown that BBB localization is disturbed by tumors, embolism, and mannitol injection, we investigated BBB-liposome permeability in an EAE rat model. Twenty young male Lewis rats received a single intradermal inoculation of guinea-pig spinal cord. The effect of the Freund's adjuvant and spinal cord alone on brain permeability were also assessed. In order to compare solution permeability and liposome localization, radioactive liposomes and, 1 h later, 99mTc-DTPA were injected intravenously. Scintigraphic acquisitions were obtained to follow the biodistribution of radioactivity in the whole body. Each rat was subjected to a first examination before inoculation and then every two days until completion and may be considered as its own control. EAE induced a previously unreported increase in global-body permeability, probably due to inflammation. Liposome brain localization and brain/heart ratio were significantly different between normal animals and those with early-stage EAE (before appearance of clinical signs) and distinguished between different disease stages in clinically patent EAE. The index of disease progression was modified earlier than with 99mTc-DTPA injection. One explanation may be particle pick-up by circulating macrophages, which cross the BBB during this pathology. For clinical applications, experiments must be confirmed on models more reliable for human multiple sclerosis.
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Enhanced permeability to nano-particulates in EAE brain may be explained by changes in the vascular system due to inflammation.
“This enhanced permeability to nano-particulates may be explained by changes in the vascular system that occurs due to the inflammation typical of the EAE brain [36], [37].”
From Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids (2011) · cites this paper as [37]
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- Authors
- Rousseau, V., Denizot, B., Le Jeune, J. J., & Jallet, P.
- Affiliations
- Université d'Angers (FR)
- Venue
- Experimental Brain Research
- Published
- 1999-03-17
- Volume
- 125
- Issue
- 3
- Pages
- 255-264
- ISSN
- 0014-4819 (ISSN-L)
- 1432-1106
- OpenAlex
- W2133172062
- Cited by
- 33
- References
- 24
- Citations by year
- 2022: 1 · 2021: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Experimental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- experimental autoimmune encephalomyelitis, multiple sclerosis, blood-brain barrier permeability, early disease detection, 99mTc-DTPA scintigraphy, disease staging, Freund's adjuvant, Lewis rats
- MeSH terms
- Animals, Urinary Bladder, Blood-Brain Barrier, Encephalomyelitis, Autoimmune, Experimental, Freund's Adjuvant, Guinea Pigs, Kidney, Liposomes, Liver, Male, Multiple Sclerosis, Myocardium, Nerve Tissue Proteins, Rats, Inbred Lew, Spinal Cord, Spleen, Tissue Distribution, Technetium Tc 99m Pentetate, Rats
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