RGD Reference Report - Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. - Rat Genome Database

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

Authors: Thored, P  Heldmann, U  Gomes-Leal, W  Gisler, R  Darsalia, V  Taneera, J  Nygren, JM  Jacobsen, SE  Ekdahl, CT  Kokaia, Z  Lindvall, O 
Citation: Thored P, etal., Glia. 2009 Jun;57(8):835-49.
RGD ID: 2313025
Pubmed: PMID:19053043   (View Abstract at PubMed)
DOI: DOI:10.1002/glia.20810   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain infarction  ISOAif1 (Rattus norvegicus)2313025; 2313025protein:increased expression:brain subventricular zone (rat)RGD 
brain infarction  IEP 2313025protein:increased expression:brain subventricular zone (rat)RGD 
middle cerebral artery infarction  ISOCd86 (Rattus norvegicus)2313025; 2313025protein:increased expression:brain subventricular zone and microglial cell (rat)RGD 
middle cerebral artery infarction  IEP 2313025protein:increased expression:brain subventricular zone and microglial cell (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aif1  (allograft inflammatory factor 1)
Cd86  (CD86 molecule)

Genes (Mus musculus)
Aif1  (allograft inflammatory factor 1)
Cd86  (CD86 antigen)

Genes (Homo sapiens)
AIF1  (allograft inflammatory factor 1)
CD86  (CD86 molecule)


Additional Information