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Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination
Abstract
CNS remyelination occurs more rapidly in young adult rats than in old rats. Since the inflammatory response initiated by demyelination is an important trigger for remyelination, we address whether ageing changes in remyelination are associated with changes in the inflammatory response. Using a toxin model of demyelination, where the inflammatory response largely comprises macrophages, we show that there is a delay in both recruitment and activation of OX-42+ and macrophage scavenger receptor B+ macrophages following demyelination in older rats (10-13 months) compared to young rats (8-10 weeks). This difference is associated with a slower onset of increased expression of several chemokine mRNAs. However, many inflammatory cytokines have similar mRNA expression patterns, with the exception of IL-1beta, IL-6 and TNF-alpha, which have prolonged expression in the older animals. Differences in IL-1beta mRNA expression, a cytokine specifically implicated in CNS remyelination, are not reflected in differences in protein expression detected by immunocytochemistry. These data relate the age-associated delay in remyelination efficiency to changes in the macrophage and inflammatory mediator response to demyelination.
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“however, white matter demyelination injury provokes a reduced macrophage response in older rodents compared to younger controls (102).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [102]
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Self-citation
Metadata
- Authors
- Zhao, C., Li, W.-W., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Franklin, Robin J.M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 27
- Issue
- 9
- Pages
- 1298-1307
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2158151457
- Cited by
- 142
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 16 · 2018: 10 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Multiple Sclerosis Society
- European Commission
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- demyelination, aging, neuroinflammation, macrophages, OX-42, chemokines, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, myelin oligodendrocyte glycoprotein, age-related decline
- MeSH terms
- Aging, Animals, Cell Count, Central Nervous System, Demyelinating Diseases, Disease Models, Animal, Female, Immunohistochemistry, Inflammation, Lysophosphatidylcholines, Macrophages, RNA, Messenger, Spinal Cord Diseases, Toxins, Biological, Gene Expression, Cytokines, Rats, Sprague-Dawley, In Situ Hybridization, Recovery of Function, Reverse Transcriptase Polymerase Chain Reaction, CD11b Antigen, Microarray Analysis, Rats
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