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

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Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain. / Laterza, Cecilia; Wattananit, Somsak; Uoshima, Naomi; Ge, Ruimin; Pekny, Roy; Tornero, Daniel; Monni, Emanuela; Lindvall, Olle; Kokaia, Zaal.

I: Experimental Neurology, Vol. 297, 01.11.2017, s. 129-137.

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Laterza, Cecilia ; Wattananit, Somsak ; Uoshima, Naomi ; Ge, Ruimin ; Pekny, Roy ; Tornero, Daniel ; Monni, Emanuela ; Lindvall, Olle ; Kokaia, Zaal. / Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain. I: Experimental Neurology. 2017 ; Vol. 297. s. 129-137.

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TY - JOUR

T1 - Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain

AU - Laterza, Cecilia

AU - Wattananit, Somsak

AU - Uoshima, Naomi

AU - Ge, Ruimin

AU - Pekny, Roy

AU - Tornero, Daniel

AU - Monni, Emanuela

AU - Lindvall, Olle

AU - Kokaia, Zaal

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Monocyte depletion

KW - Neurogenesis

KW - Reactive gliosis

U2 - 10.1016/j.expneurol.2017.07.012

DO - 10.1016/j.expneurol.2017.07.012

M3 - Article

VL - 297

SP - 129

EP - 137

JO - Neurodegeneration

JF - Neurodegeneration

SN - 0014-4886

ER -