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

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 radiation-induced brain injury and hemorrhagic stroke, and offers new insights into the therapeutic role of NeuroD1 in delayed brain injury.