Ginkgolide B promotes spontaneous recovery and enhances endogenous netrin‐1 after neonatal hypoxic–ischemic brain damage

Abstract Objectives Perinatal hypoxic–ischemic encephalopathy (HIE) is a condition that can lead to long‐term cognitive, motor, and behavioral impairments in newborns. Although brain hypothermia therapy is currently the standard treatment for HIE, it does not provide complete neuroprotection. As a result, there is a need to explore additional therapies to enhance treatment outcomes. This study aims to investigate the potential role of Ginkgolide B (GB) in promoting neuroplasticity and facilitating spontaneous recovery after HIE. Methods In this study, we employed a neonatal rat model of HIE to investigate the effects of GB on spontaneous recovery. GB treatment was initiated 24 h after hypoxia and administered continuously for a duration of 14 days. We evaluated several outcome measures after the treatment period, including spontaneous behavioral recovery and brain repair. Additionally, we quantified the levels of netrin‐1 in both plasma and the peri‐ischemic zone after the occurrence of HIE. Results We found that GB treatment significantly facilitated spontaneous behavioral recovery in the HIE pups. Furthermore, cognitive function was restored, and brain tissue repair had a noticeable acceleration. We observed increased cell proliferation in the subventricular, stratum, and subgranular zones. Of particular interest, we observed elevated levels of netrin‐1 in both plasma and the ischemic penumbra following GB treatment. Conclusion Our findings suggest that GB promotes neuroplasticity and enhances spontaneous recovery in newborns affected by HIE. The observed upregulation of netrin‐1 may be crucial in mediating these effects. These results highlight the promising potential of GB as a post‐HIE therapy, particularly in enhancing spontaneous recovery and improving long‐term outcomes.