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

IF 1.7 4区医学 Q3 DEVELOPMENTAL BIOLOGY

International Journal of Developmental Neuroscience Pub Date : 2023-09-29 DOI:10.1002/jdn.10301

Aiming Chen, Jun Hua, Jun Yuan, Yajuan Feng, Fengzhan Chen, Yongqin Zhou, Ting Han, Weiwei Jiang, Huiping Chen

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引用次数: 0

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.

Abstract Image

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银杏内酯B促进新生儿缺氧缺血性脑损伤后的自发恢复并增强内源性netrin-1。

目的：围产期缺氧缺血性脑病（HIE）是一种可导致新生儿长期认知、运动和行为障碍的疾病。尽管脑低温治疗目前是HIE的标准治疗方法，但它并不能提供完全的神经保护。因此，有必要探索其他疗法来提高治疗效果。本研究旨在探讨银杏内酯B（GB）在促进HIE后神经可塑性和促进自然恢复方面的潜在作用。GB治疗开始24 缺氧后h，持续给药14 天。我们评估了治疗期后的几个结果指标，包括自发行为恢复和大脑修复。此外，我们还定量了HIE发生后血浆和缺血周围区域的netrin-1水平。结果：我们发现GB治疗显著促进了HIE幼崽的自发行为恢复。此外，认知功能得到恢复，脑组织修复明显加速。我们观察到室下、层和颗粒下区域的细胞增殖增加。特别令人感兴趣的是，我们观察到GB治疗后血浆和缺血半暗带中netrin-1水平升高。结论：我们的研究结果表明，GB可促进HIE新生儿的神经可塑性并促进其自发恢复。观察到的netrin-1的上调可能在介导这些效应中至关重要。这些结果突出了GB作为HIE后治疗的潜力，特别是在增强自发恢复和改善长期结果方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Developmental Neuroscience 医学-发育生物学

CiteScore

3.30

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.