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Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke
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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From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [66]
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26 Neurogenesis following Stroke Affecting the Adult BrainPreprint
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“However, increasing evidence showed that microglia activation could also be beneficial through attenuating neuronal apoptosis, enhancing neurogenesis, and promoting functional recovery after cerebral ischemia (Faustino et al., 2011; LalancetteHebert et al., 2007; Neumann et al., 2008; Thored et al., 2009).”
Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke
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“In addition, the long-term accumulation of M2-polarized microglia also implies a supportive role for continuous neurogenesis after stroke (Thored et al., 2009), and M2 polarization isessential for efficient remyelination in CNS regeneration (Miron et al.”
BackgroundKreisel, T., Frank, M. G., Licht, T., Reshef, R., Ben-Menachem-Zidon, O., Baratta, M. V., Maier, S. F., & Yirmiya, R. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.155 · Cited by 663
Metadata
- 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
- ORCID
- 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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