Abstract

TGFß 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-ß1 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 TGFß signaling after stroke, and whether its signaling pattern is altered by gender and aging.We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFß reporter mice to get a readout of TGFß responses after stroke in real time. To determine which cell type is the source of increased TGFß production after stroke, brain sections were stained with an anti-TGFß antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFß after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFß signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.TGFß 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 TGFß signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFß after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFß signaling after stroke. TGFß signaling in neurons and oligodendrocytes did not undergo marked changes.We found that TGFß signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFß signaling in response to post-stroke increases in TGFß. Therefore increased TGFß after stroke likely regulates glial scar formation and the immune response to stroke.

View details for DOI 10.1186/1742-2094-7-62

View details for PubMedID 20937129