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Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke.

Thored, Pär LU ; Heldmann, Ursula LU ; Gomes-Leal, Walace; Gisler, Ramiro LU ; Darsalia, Vladimer LU ; Taneera, Jalal LU ; Nygren, Jens LU ; Jacobsen, Sten Eirik W LU ; Ekdahl Clementson, Christine LU and Kokaia, Zaal LU , et al. (2009) In GLIA 57. p.835-849
Abstract
Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks... (More)
Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri-infarct striatum. Numbers of microglia expressing markers of antigen-presenting cells (MHC-II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short- and long-term increase (at 1 and 6 weeks postinfarct) of insulin-like growth factor-1 (IGF-1) gene expression was detected in SVZ tissue. Elevated numbers of IGF-1-expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF-1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. (c) 2008 Wiley-Liss, Inc. (Less)
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GLIA
volume
57
pages
835 - 849
publisher
John Wiley & Sons
external identifiers
  • wos:000265572300004
  • pmid:19053043
  • scopus:67649838794
ISSN
1098-1136
DOI
10.1002/glia.20810
language
English
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yes
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e2feda5a-f913-4d18-8922-7397145f3104 (old id 1276500)
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http://www.ncbi.nlm.nih.gov/pubmed/19053043?dopt=Abstract
date added to LUP
2009-01-09 09:21:37
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2017-11-19 04:17:56
@article{e2feda5a-f913-4d18-8922-7397145f3104,
  abstract     = {Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri-infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri-infarct striatum. Numbers of microglia expressing markers of antigen-presenting cells (MHC-II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short- and long-term increase (at 1 and 6 weeks postinfarct) of insulin-like growth factor-1 (IGF-1) gene expression was detected in SVZ tissue. Elevated numbers of IGF-1-expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF-1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. (c) 2008 Wiley-Liss, Inc.},
  author       = {Thored, Pär and Heldmann, Ursula and Gomes-Leal, Walace and Gisler, Ramiro and Darsalia, Vladimer and Taneera, Jalal and Nygren, Jens and Jacobsen, Sten Eirik W and Ekdahl Clementson, Christine and Kokaia, Zaal and Lindvall, Olle},
  issn         = {1098-1136},
  language     = {eng},
  pages        = {835--849},
  publisher    = {John Wiley & Sons},
  series       = {GLIA},
  title        = {Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke.},
  url          = {http://dx.doi.org/10.1002/glia.20810},
  volume       = {57},
  year         = {2009},
}