Dynamic expression of type III collagen in the lesion core of post-ischemic brain colocalizing with angiogenesis and lipid droplets during fibrotic scar formation

Abstract

Two distinct types of scars are formed in the brain after ischemic stroke: glial scar and fibrotic scar. Dynamic collagen expression has been well-studied in peripheral tissue wound healing. However, it is less understood in the post-ischemic brain. This study investigated the spatiotemporal dynamics of type III collagen (Col III) in the lesion core of mouse photothrombotic stroke model. First, RNA-seq analysis was performed to examine the transcriptional profiling of the lesion core at 14 days post-injury (dpi). Collagen 3a1, encoding Col III, was one of the most induced genes. Gene ontology (GO) enrichment analysis revealed that inflammatory responses are primarily activated, as well as phagosome, extracellular matrix (ECM) organization, and vasculature development pathways. In the subacute stage (at 3–14 dpi), Col III immunoreactivity was higher than Col I, which surrounded the penetrating vasculatures from the meninges. Late (14–28 dpi), the fibrillar mesh of Col III was prominent in which Iba1-positive phagocytes stored lipid droplets (LDs). In vivo injection of collagen synthesis inhibitor reduced penetrating vasculatures, decreased LD accumulation, and increased the infarcted area. Collectively, these results suggest that Col III is dynamically expressed in the lesion core during fibrotic scar formation colocalizing with angiogenesis and LDs.