中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 2872-2883.doi: 10.4103/NRR.NRR-D-24-01067

• 原著:脑损伤修复保护与再生 • 上一篇    

基于NeuroD1原位神经再生的治疗放射性脑损伤

  

  • 出版日期:2026-07-15 发布日期:2025-10-21
  • 基金资助:
    该项工作受到广州市科技计划、广东省重点领域研发计划、“珠江人才计划”引进创新团队、STI 2030重大项目、国家自然科学基金、广东省基础与应用基础研究基金和中山大学孙逸仙纪念医院逸仙青年启航基金的大力支持。

NeuroD1-based in situ neural regeneration for the treatment of radiation-induced brain injury

Xudong Yan1, #, Ke Zhong2, 3, 4, #, Meijuan Zhou5 , Jiao Chen1 , Yajie Sun1, *, †, Yamei Tang2, 3, *, Gong Chen1, *, Yongteng Xu2, 3, *   

  1. 1 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China;  2 Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China;  3 Brain Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China;  4 Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China;  5 Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China  †Present address: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Online:2026-07-15 Published:2025-10-21
  • Contact: Yongteng Xu, MS, xuyt5@mail2.sysu.edu.cn; Gong Chen, PhD, gongchen@jnu.edu.cn; Yamei Tang, PhD, tangym@mail.sysu.edu.cn; Yajie Sun, PhD, sunyajiecn@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81925031 (to YT), 82330099 (to YT), 82404189 (to KZ); the Key-Area Research and Development Program of Guangdong Province, No. 2023B0303040003 (to YT); STI 2030-Major Projects, No. 2022ZD0211603 (to YT); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology, No. 202206060002 (to GC and YS); Science and Technology Project of Guangdong Province, No. 2018B030332001 (to GC); Guangdong Provincial Pearl River Project, No. 2021ZT09Y552 (to GC); the Guangdong Basic and Applied Basic Research Foundation, No. 2022A1515110189 (to KZ); and Sun Yat-sen Pilot Scientific Research Fund, No. YXQH202427 (to KZ).

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摘要：

放射性脑损伤是头颈部肿瘤放射治疗最严重的并发症，其预防和治疗方法有限。原位神经再生技术在多种神经退行性疾病和神经创伤中显示出潜在的治疗效果。因此，实验对放射性脑损伤小鼠模型中行过表达神经转录因子NeuroD1的原位神经再生技术。结果显示，这种方法可将损伤部位中的反应性星形胶质细胞转分化为神经元，增加神经元密度，保护内源性神经元，减少小胶质细胞活化、外周CD8+T细胞浸润以及血管生成，从而缩小病变体积。此外，实验进一步通过普通转录组测序探索了NeuroD1原位神经再生技术的潜在机制，发现神经发生相关基因上调，免疫反应相关和血管生成相关基因下调。此外将NeuroD1原位神经再生技术应用于丘脑出血性脑卒中小鼠模型中，也可将反应性星形胶质细胞转化为神经元，并抑制小胶质细胞的活化。综上，NeuroD1原位神经再生技术为治疗放射性脑损伤和出血性脑卒中提供了一种新方法，也为在延迟性脑损伤治疗提供了新思路。

https://orcid.org/0000-0001-8989-9048 (Yongteng Xu); https://orcid.org/0000-0002-1857-3670 (Gong Chen);

https://orcid.org/0000-0002-6353-6107 (Yamei Tang); https://orcid.org/0009-0009-8371-671X (Yajie Sun)

关键词: 放射性脑损伤, 出血性脑卒中, 原位神经再生, 转分化, NeuroD1, 反应性星形胶质细胞, 神经炎症, 血管生成, 磁共振成像, 普通转录组测序

Abstract: Radiation-induced brain injury remains one of the most severe complications of radiotherapy for head and neck tumors, with limited options for prevention and treatment. In situ neural regeneration technology has demonstrated promising therapeutic effects in various neurodegenerative and neurotrauma conditions. In this study, we overexpressed the neural transcription factor NeuroD1 using in situ neural regeneration technology in a radiation-induced brain injury mouse model. This approach converted reactive astrocytes into neurons, increased neuronal density, protected endogenous neurons, decreased microglial activation, reduced peripheral CD8+ T cell infiltration, and diminished angiogenesis in the injured area, leading to a significant reduction in lesion volume. Additionally, we explored the potential mechanisms of NeuroD1 in situ neural regeneration technology through bulk RNA sequencing, which showed an upregulation of neurogenesis-related genes and a downregulation of immune response–related and angiogenesis-related genes. Furthermore, our findings suggested that NeuroD1 in situ neural regeneration technology converted reactive astrocytes into neurons and reduced microglial activation in a thalamic hemorrhagic stroke mouse model. In summary, this study supports NeuroD1 in situ neural regeneration technology as a potential therapeutic approach for treating radiationinduced brain injury and hemorrhagic stroke, and offers new insights into the therapeutic role of NeuroD1 in delayed brain injury.

Key words: angiogenesis, bulk RNA sequencing, hemorrhagic stroke, in situ neural regeneration, magnetic resonance imaging, NeuroD1, neuroinflammation, radiation-induced brain injury, reactive astrocytes, transdifferentiation