干细胞外泌体递送脑源性神经营养因子治疗急性脑损伤的研究进展OA

Acute brain injury(ABI)is characterized by high incidence and disability rates,involving com-plex pathological mechanisms that necessitate novel neuroprotective and regenerative strategies.Although brain-derived neurotrophic factor(BDNF)plays a well-established role in regulating neuronal survival,impro-ving synaptic plasticity,and attenuating neuroinflammation,its clinical application is hindered by its short half-life and difficulty in crossing the blood-brain barrier(BBB).In recent years,stem cell-derived exosomes have emerged as ideal carriers for delivering BDNF,owing to their natural nanoscale size,low immunogenicity and high BBB permeability.This review focuses on the neuroprotective mechanisms of BDNF in ABI and the appli-cation potential of stem cell-derived exosomes for targeted BDNF delivery.It elaborates on the biological char-acteristics and engineering strategies of stem cell-derived exosomes,summarizes the research progress on exo-some-based BDNF delivery systems in ABI treatment,and analyzes key issues and challenges in their clinical translation.Despite the promising therapeutic potential demonstrated by extensive preclinical studies,this de-livery system remains challenged by suboptimal exosome drug-loading efficiency and brain-targeting preci-sion,immature scalable production and standardized preparation protocols,undefined regulatory classification and evaluation frameworks,and a lack of large animal models and comprehensive preclinical safety evidence.Future efforts should leverage multi-omics technologies to elucidate the underlying molecular networks,devel-op biomimetic or brain-targeted delivery systems,and integrate tissue engineering techniques.Furthermore,promoting clinical translation through standardized,multi-center preclinical validation will provide precise and translatable therapeutic strategies for neural repair following ABI.