TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

Kristian Doyle, Egle Cekanaviciute, Lauren E. Mamer, Marion S. Buckwalter

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Background: TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging.Methods: We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.Results: TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes.Conclusions: We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

Original languageEnglish (US)
Article number62
JournalJournal of Neuroinflammation
Volume7
DOIs
StatePublished - Oct 11 2010
Externally publishedYes

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Astrocytes
Stroke
Brain
Microglia
Middle Cerebral Artery Infarction
Macrophages
Oligodendroglia
Neurons
Neuroglia
Cicatrix
Immune System
Anti-Idiotypic Antibodies
Up-Regulation
Endothelial Cells

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

Cite this

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. / Doyle, Kristian; Cekanaviciute, Egle; Mamer, Lauren E.; Buckwalter, Marion S.

In: Journal of Neuroinflammation, Vol. 7, 62, 11.10.2010.

Research output: Contribution to journalArticle

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