Angiogenesis and Ischemic Stroke

Stroke is a leading cause of death and disability in adults globally, with its associated health burden rising steadily over recent decades. This review aims to systematically summarize the diverse cell types and related signaling pathways that modulate angiogenesis after cerebral ischemia, and to highlight the urgency of exploring effective therapeutic strategies for ischemic stroke based on angiogenic mechanisms.

A systematic literature search was conducted across multiple databases, including PubMed, Google Scholar, and Web of Science. The search utilized the keywords "cerebral ischemia" and "angiogenesis," and was limited to publications from 2020 to 2025. Clinical trials were prioritized as the primary source of evidence. When relevant clinical data were limited or absent, animal experimental research articles were also considered to ensure the quality and consistency of the included literature.

Angiogenesis exerts a critical protective effect during the pathophysiological process of stroke: it restores cerebral blood flow, promotes nerve regeneration and functional recovery, and neovascularization in the perinfarct area markedly improves post-ischemic hemodynamic status. Multiple cell types (e.g., bone marrow-derived cells, endothelial progenitor cells) and key signaling pathways (e.g., PI3K/AKT, JAK2/STAT3, HIF-1α/VEGF) are associated with the regulation of angiogenesis, with such associations yet to be validated as definitive causal relationships.

Although current preclinical studies have preliminarily elucidated the regulatory roles of key signaling pathways in post-ischemic angiogenesis and have identified scientific issues that require further investigation, these studies have only confirmed a correlation between signaling pathways and angiogenesis and have not yet established a clear causal mechanism. Therefore, conducting more rigorous mechanistic and clinical translational studies has become the core task at this stage.

Promoting angiogenesis is an imperative and promising approach for IS therapy. Further in-depth exploration of the cellular and molecular mechanisms of post-ischemic angiogenesis will provide novel therapeutic targets and strategies for improving the clinical outcomes of stroke patients, addressing the unmet clinical needs of this devastating disease.