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Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke.

Inacio, Ana LU ; Ruscher, Karsten LU ; Leng, Lin; Bucala, Richard and Deierborg, Tomas LU (2011) In Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Dec. p.1093-1106
Abstract
Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels... (More)
Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 November 2010; doi:10.1038/jcbfm.2010.194. (Less)
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published
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in
Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
Dec
pages
1093 - 1106
publisher
Nature Publishing Group
external identifiers
  • wos:000289064500013
  • pmid:21063426
  • scopus:79953269823
ISSN
1559-7016
DOI
10.1038/jcbfm.2010.194
language
English
LU publication?
yes
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db64dd0c-bcc1-421b-bcf3-6251399f651a (old id 1732114)
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http://www.ncbi.nlm.nih.gov/pubmed/21063426?dopt=Abstract
date added to LUP
2010-12-01 11:29:16
date last changed
2017-11-12 04:09:52
@article{db64dd0c-bcc1-421b-bcf3-6251399f651a,
  abstract     = {Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 November 2010; doi:10.1038/jcbfm.2010.194.},
  author       = {Inacio, Ana and Ruscher, Karsten and Leng, Lin and Bucala, Richard and Deierborg, Tomas},
  issn         = {1559-7016},
  language     = {eng},
  pages        = {1093--1106},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
  title        = {Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke.},
  url          = {http://dx.doi.org/10.1038/jcbfm.2010.194},
  volume       = {Dec},
  year         = {2011},
}