Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 2872-2883.doi: 10.4103/NRR.NRR-D-24-01067

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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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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