Therapeutic strategies for the ischemic stroke recovery: The crosstalk between neurogenesis and angiogenesis

Stroke is a cerebrovascular disorder characterized by focal or global cerebral tissue damage, which ranks among the leading causes of mortality and disability globally. Ischemic stroke accounts for approximately 65.3% of all stroke cases. Currently, therapeutic strategies for ischemic stroke remain suboptimal. The concept of the neurovascular unit emphasizes the integrated regulation of neural and vascular components, and neurogenesis and angiogenesis represent the core neurovascular responses during ischemic stroke recovery. These two processes exhibit intimate crosstalk, forming a neurovascular collaborative repair mechanism that is precisely regulated by multiple cytokines and key signaling pathways. This review systematically summarizes the underlying mechanisms of this crosstalk and its pivotal role in post-stroke tissue repair and neurological functional recovery. Despite significant advances in this field, current research still has notable limitations, including insufficient elucidation of the interactions among multiple factors and pathways, unclear dynamic patterns of crosstalk across different recovery stages, and a lack of correlation between preclinical animal models and clinical scenarios. Future investigations should employ advanced technologies (e.g., single-cell sequencing) to further explore crosstalk mechanisms, focus on crosstalk associated with neural cell transdifferentiation, and establish preclinical models that closely mimic clinical conditions. Targeting the crosstalk between neurogenesis and angiogenesis represents a promising preclinical approach for precise therapeutic intervention. Although current evidence is largely derived from animal models, this strategy holds potential to address some of the current clinical limitations and improve neurological functional recovery and long-term quality of life in patients with ischemic stroke, pending rigorous validation in future clinical studies.