Abstract | OBJECTIVE: METHODS: To address mechanisms of inflammation, we studied microglial activation in human ALD (10 autopsies) and lysophosphatidylcholine (C24:0) injection into the parietal cortex of mice. RESULTS: Unexpectedly, we found a zone lacking microglia within perilesional white matter, immediately beyond the actively demyelinating lesion edge. Surrounding this zone we observed clusters of activated and apoptotic microglia within subcortical white matter. Lysophosphatidylcholine (C24:0) injection in mice led to widespread microglial activation and apoptosis. INTERPRETATION: Our data suggest that the distinct mononuclear phagocytic cell response seen in cerebral X-ALD results, at least in part, from aberrant signaling to cognate receptors on microglia. Our findings support a hypothesis that microglial apoptosis in perilesional white matter represents an early stage in lesion evolution and may be an appropriate target for intervention in X-ALD patients with evidence of cerebral demyelination.
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Authors | Florian S Eichler, Jia-Qian Ren, Michael Cossoy, Anna M Rietsch, Sameer Nagpal, Ann B Moser, Matthew P Frosch, Richard M Ransohoff |
Journal | Annals of neurology
(Ann Neurol)
Vol. 63
Issue 6
Pg. 729-42
(Jun 2008)
ISSN: 1531-8249 [Electronic] United States |
PMID | 18571777
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Inflammation Mediators
- Lysophosphatidylcholines
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Topics |
- Adolescent
- Adrenoleukodystrophy
(metabolism, pathology, physiopathology)
- Adult
- Animals
- Apoptosis
- Biomarkers
- Chemotaxis, Leukocyte
(genetics)
- Child
- Disease Progression
- Encephalitis
(genetics, pathology, physiopathology)
- Gliosis
(genetics, pathology, physiopathology)
- Hereditary Central Nervous System Demyelinating Diseases
(metabolism, pathology, physiopathology)
- Humans
- Inflammation Mediators
(pharmacology)
- Lysophosphatidylcholines
(pharmacology)
- Mice
- Mice, Inbred C57BL
- Microglia
(pathology)
- Myelin Sheath
(metabolism, pathology)
- Phagocytosis
(physiology)
- Time Factors
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