Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor
(2009) In The Journal of Neuroscience 29(5). p.1319-1330- Abstract
- Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By using in situ hybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type... (More)
- Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By using in situ hybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial-not leukocyte-derived TNF. In addition, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglial-derived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1311381
- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- neuroprotection, chimeric mice, knock-out mice, cytokines, neurodegeneration, behavior
- in
- The Journal of Neuroscience
- volume
- 29
- issue
- 5
- pages
- 1319 - 1330
- publisher
- Society for Neuroscience
- external identifiers
-
- wos:000263072400008
- scopus:59649117102
- pmid:19193879
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.5505-08.2009
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
- id
- 4a2dff72-b6a9-4c9d-9ec6-00ce456c6b9a (old id 1311381)
- date added to LUP
- 2016-04-01 14:24:35
- date last changed
- 2023-09-03 14:02:14
@article{4a2dff72-b6a9-4c9d-9ec6-00ce456c6b9a,
abstract = {{Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By using in situ hybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial-not leukocyte-derived TNF. In addition, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglial-derived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia.}},
author = {{Lambertsen, Kate Lykke and Clausen, Bettina Hjelm and Babcock, Alicia Anne and Gregersen, Rikke and Fenger, Christina and Nielsen, Helle Hvilsted and Haugaard, Laila Skov and Wirenfeldt, Martin and Nielsen, Marianne and Dagnaes-Hansen, Frederik and Bluethmann, Horst and Faergeman, Nils Joakim and Meldgaard, Michael and Deierborg, Tomas and Finsen, Bente}},
issn = {{1529-2401}},
keywords = {{neuroprotection; chimeric mice; knock-out mice; cytokines; neurodegeneration; behavior}},
language = {{eng}},
number = {{5}},
pages = {{1319--1330}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience}},
title = {{Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.5505-08.2009}},
doi = {{10.1523/JNEUROSCI.5505-08.2009}},
volume = {{29}},
year = {{2009}},
}