Cited by 379Neurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

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

Thored, Pär, Heldmann, Ursula, Gomes‐Leal, Walace, Gisler, Ramiro, Darsalia, Vladimer, Taneera, Jalal, Nygren, Jens M., Jacobsen, Sten‐Eirik W. +3 more·2009·Glia

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.

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Crossref · 10.1002/glia.20810

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Authors
Thored, P., Heldmann, U., Gomes‐Leal, W., Gisler, R., Darsalia, V., Taneera, J., Nygren, J. M., Jacobsen, S. W., Ekdahl, C. T., Kokaia, Z., & Lindvall, O.
Affiliations
Lund University (SE)
Corresponding author
Lindvall, Olle
Venue
Glia
Publisher
Wiley
Published
2008-12-02
Volume
57
Issue
8
Pages
835-849
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W2114303594
Cited by
378
References
61
Citations by year
2026: 6 · 2025: 14 · 2024: 9 · 2023: 15 · 2022: 18 · 2021: 30 · 2020: 22 · 2019: 26 · 2018: 19 · 2017: 21 · 2016: 25 · 2015: 21 · 2014: 29 · 2013: 29 · 2012: 37
FWCI
5.64
Type
journal article
Language
en
Open access
closed
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
microglia, subventricular zone, ischemic stroke, adult neurogenesis, neuroblast migration, striatum, microglial activation, insulin-like growth factor I, neurogenesis, MHC class II, CD86, antigen-presenting cells, middle cerebral artery occlusion, stroke recovery
MeSH terms
Analysis of Variance, Animals, Antigen-Presenting Cells, Calcium-Binding Proteins, Cell Movement, Corpus Striatum, Disease Models, Animal, Insulin-Like Growth Factor I, Functional Laterality, Male, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Phenotype, Time Factors, Bone Marrow Transplantation, Rats, Wistar, Leukocyte Common Antigens, Microglia, Stroke, Lateral Ventricles, Cell Proliferation, Green Fluorescent Proteins, Mice, Rats, Ectodysplasins, Neurogenesis

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