Fibroblast growth factors in ischemic stroke: Therapeutic potential and clinical challenges

Ischemic stroke is a leading cause of global mortality and long-term disability, with limited therapeutic options. Increasing evidence from experimental studies suggests that fibroblast growth factors (FGFs) play important roles in regulating key biological processes involved in brain repair following ischemia. This review examines the existing evidence to understand the functional roles of FGFs in ischemic stroke, highlighting findings from in vivo and in vitro models, as well as outcomes from clinical investigations. FGFs contribute to neuroprotection by supporting neuronal survival, modulating inflammatory responses, preserving blood-brain barrier (BBB) integrity, and enhancing angiogenesis. Despite promising data from experimental models, clinical translation of FGF-based therapies has proven challenging. Clinical trials have encountered issues such as safety concerns, particularly regarding optimal dosing and the risk of adverse effects, which complicates treatment response. These limitations highlight the complexity of translating FGF-based therapies into clinical practice in stroke treatment. Additionally, emerging FGF biomarkers may help predict therapeutic responses and guide patient selection and diagnosis. Future research should focus on optimizing delivery systems, identifying therapeutic windows, and improving clinical trial design, as successful clinical translation of FGF therapies relies on resolving subtype-specificity and refining delivery strategies to ensure targeted and effective treatment. Therefore, gaining a deeper understanding of the timing and context of FGF activity following ischemic stroke could pave the way for successful clinical applications, such as early neuroprotection, preservation of BBB integrity, and reduction of neuroinflammation. This understanding could also support the development of more targeted and effective interventions for ischemic stroke.