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Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain

Laterza, Cecilia LU ; Wattananit, Somsak LU orcid ; Uoshima, Naomi ; Ge, Ruimin LU ; Pekny, Roy ; Tornero, Daniel LU ; Monni, Emanuela LU ; Lindvall, Olle LU and Kokaia, Zaal LU orcid (2017) In Experimental Neurology 297. p.129-137
Abstract

Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum. Blocking monocyte recruitment did not alter the volume of the ischemic lesion but gave rise to reduced astrocyte activation... (More)

Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum. Blocking monocyte recruitment did not alter the volume of the ischemic lesion but gave rise to reduced astrocyte activation in SVZ and adjacent striatum, which could contribute to the improved neuroblast survival. A similar decrease of astrocyte activation was found in and around human induced pluripotent stem cell (iPSC)-derived NSPCs transplanted into striatum at one week after stroke in monocyte-depleted mice. However, there was no effect on neurogenesis in the graft as determined 8 weeks after implantation. Our findings demonstrate, for the first time, that a specific cellular component of the early inflammatory reaction in SVZ and adjacent striatum following stroke, i.e., infiltrating monocytes, compromises the short-term neurogenic response neurogenesis from endogenous NSPCs.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Monocyte depletion, Neurogenesis, Reactive gliosis
in
Experimental Neurology
volume
297
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:28746827
  • wos:000412617300013
  • scopus:85027497828
ISSN
0014-4886
DOI
10.1016/j.expneurol.2017.07.012
language
English
LU publication?
yes
id
2fa54e51-b96a-4d1b-8809-d6423ab5fdee
date added to LUP
2017-09-05 14:46:15
date last changed
2025-02-04 02:53:51
@article{2fa54e51-b96a-4d1b-8809-d6423ab5fdee,
  abstract     = {{<p>Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum. Blocking monocyte recruitment did not alter the volume of the ischemic lesion but gave rise to reduced astrocyte activation in SVZ and adjacent striatum, which could contribute to the improved neuroblast survival. A similar decrease of astrocyte activation was found in and around human induced pluripotent stem cell (iPSC)-derived NSPCs transplanted into striatum at one week after stroke in monocyte-depleted mice. However, there was no effect on neurogenesis in the graft as determined 8 weeks after implantation. Our findings demonstrate, for the first time, that a specific cellular component of the early inflammatory reaction in SVZ and adjacent striatum following stroke, i.e., infiltrating monocytes, compromises the short-term neurogenic response neurogenesis from endogenous NSPCs.</p>}},
  author       = {{Laterza, Cecilia and Wattananit, Somsak and Uoshima, Naomi and Ge, Ruimin and Pekny, Roy and Tornero, Daniel and Monni, Emanuela and Lindvall, Olle and Kokaia, Zaal}},
  issn         = {{0014-4886}},
  keywords     = {{Monocyte depletion; Neurogenesis; Reactive gliosis}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{129--137}},
  publisher    = {{Elsevier}},
  series       = {{Experimental Neurology}},
  title        = {{Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain}},
  url          = {{http://dx.doi.org/10.1016/j.expneurol.2017.07.012}},
  doi          = {{10.1016/j.expneurol.2017.07.012}},
  volume       = {{297}},
  year         = {{2017}},
}