Vascular obstruction often causes inadequate oxygen and nutrient supply to the brain. This deficiency results in cerebral ischemic injury, which significantly impairs neurological function. This review aimed to explore the neuroprotective and regenerative effects of nerve growth factor (NGF) in cerebral ischemic injury. NGF, a crucial neurotrophic factor, could inhibit neuronal apoptosis, reduce inflammatory responses, and promote axon regeneration and angiogenesis through its interaction with TrkA, a high-affinity receptor. These functions were closely related to the activation of Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) and Mitogen-Activated Protein Kinase (MAPK) pathways. Moreover, the mechanisms of NGF in the acute and recovery phases, along with the strategies to enhance its therapeutic effects using delivery systems (such as intranasal administration, nanovesicles, and gene therapy) were also summarized. Although NGF shows great potential for clinical application, its delivery efficiency and long-term safety still need more research and improvements. Future research should focus on exploring the specific action mechanism of NGF, optimizing the delivery strategy, and evaluating its long-term efficacy and safety to facilitate its clinical transformation in cerebral ischemic stroke.
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