Angiogenesis and neuronal remodeling after ischemic stroke

Abstract

Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models. This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke. Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit. In this mini-review, we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia. Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery. Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery. First, new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling. Second, blood vessels are thought to enhance neurogenesis in three stages: 1) Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals, 2) microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen, nutrients, and soluble factors as well as serving as a scaffold for migration, and 3) oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons. Thus, the regions of angiogenesis and surrounding tissue may be coupled, representing novel treatment targets.

Single Cell Analysis in Vascular Biology

“…Decreased blood perfusion in the brain can impair neural function and cause neurovascular disorders (102), and complete blockage of blood and vascular failure results in stroke (103). In addition, vascular cells respond to ischemic injury, which promotes angiogenesis, vascular remodeling, and activation of the neurovascular stem cell niche (104)(105)(106)(107). Therefore, maintenance of proper blood circulation via mature arteries and veins is critical for healthy brain function.…”

A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation

“…In addition, the OGD condition was confirmed to upregulate PPARγ, which mediates such a monocyte/macrophage polarisation from the pro-inflammatory to the protective phenotype 30 . We speculate the pleiotropic effects of OGD-PBMCs, which include the paracrine actions of the remodelling factors, to promote angiogenesis and axonal outgrowth 9,37–40 (Fig. 7(i)).…”

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

“…Their findings indicated that ischemic stroke induced significant transcriptome changes in monocytes and macrophages in the post-stroke brain; however, only moderate changes were observed in the blood samples of the ischemic stroke group when compared with the control group. Further, macrophages in the post-ischemic stroke brain display unique transcriptome characteristics, robustly favoring neurovascular plasticity 5 days after ischemic stroke, suggesting that macrophages in the brain upregulate genes related with neovascularization, such as oncostatin M (Osm) (143), osteopontin (Spp1) (144), growth differentiation factor 15 (GDF15) (145), vascular endothelial growth factor (VEGF) (146), and fibroblast growth factor 1 (FGF1) (147). Surprisingly, lower angiogenesis and neurogenesis were verified in myeloid cellspecific peroxisome proliferator-activated receptor γ (PPARγ) knockout (mKO) mice than in wild-type mice 5 days after ischemic stroke.…”