Advances in research on the role of VEGF family members in ischemic stroke.

Ischemic stroke involves two interrelated pathological processes: primary ischemic brain injury and secondary cerebral ischemia-reperfusion (CI/R) injury. This condition has become a global health issue; however, effective pharmacotherapies for ameliorating cerebral ischemia (CI) and CI/R injury remain critically lacking. Members of the vascular endothelial growth factor (VEGF) family, recognized as key signaling molecules, play pivotal roles in various physiological and pathological processes, including angiogenesis, neuroprotection, neuroinflammation, and vascular permeability. Recent studies have revealed that several members of the VEGF family may mitigate CI or CI/R injury through mechanisms such as promoting angiogenesis, inhibiting neuronal apoptosis, and counteracting neuroinflammation. Paradoxically, these molecules can also exacerbate ischemic and I/R-induced brain damage by promoting blood-brain barrier disruption and intensifying inflammatory responses post-stroke. This narrative review evaluates the dual roles of distinct VEGF family members in CI and I/R injury, focusing on elucidating their underlying mechanisms. The review aims to provide a theoretical framework for optimizing VEGF-targeted therapeutic strategies, thereby maximizing neuroprotective efficacy while minimizing adverse effects in stroke treatment.