http://www.sciencedirect.com/science/article/pii/S0014488617301863
Highlights
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- Depletion of circulating monocytes after stroke enhances striatal neurogenesis
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- Infiltrating monocytes compromise survival of newly generated neuroblasts
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- Depletion of circulating monocytes after stroke attenuates reactive gliosis
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- Infiltrating monocytes do not affect neurogenesis from grafted human NSPCs
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 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.
Abbreviations
- GFAP, glial fibrillary acidic protein;
- iPSCs, induced pluripotent stem cells;
- MCAO, middle cerebral artery occlusion;
- MCP-1, monocyte chemoattractant protein-1;
- MDMs, monocyte-derived macrophages;
- NSPCs, neural stem/progenitor cells;
- OB, olfactory bulb;
- OPN, osteopontin;
- SVZ, subventricular zone
Keywords
- Neurogenesis;
- Monocyte depletion;
- Reactive gliosis
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