Altered neuroinflammaory transcriptomic profile in the hippocampal dentate gyrus three weeks after lateral fluid percussion injury in rats

Traumatic brain injury (TBI) is a major source of disability worldwide with cognitive and memory deficits being pervasive after injury. The hippocampus, a major structure involved in learning and memory, is particularly vulnerable to TBI, and cellular dysfunction within the hippocampal dentate gyrus is believed to be a major contributor to cognitive deficits after TBI. However, there is a little known about the transcriptomic changes occurring directly within the dentate gyrus at subacute-to-chronic timepoints after TBI. To address this, we performed bulk RNA sequencing and single nuclei RNA sequencing of the isolated dentate gyrus three weeks after lateral fluid percussion injury in male rats. We report here that there is evidence of an ongoing neuroinflammatory response marked by increased neuroinflammatory genes that implicate various neuroinflammatory pathways that are associated with a subset of microglia and astrocyte populations. R-code available at "https://github.com/NgwenyaLab/DeSana_and_Alfawares_2025" Male sprague dawley rats received a traumatic brain injury by lateral fluid percussion injury and then were euthanized 3 weeks after injury. The brain was dissected out and ipsilateral dentate gyrus was isolated and processed for bulk RNA sequencing (n = 3/group) or single nuclei RNA sequencing (n = 2/group)

创伤性脑损伤（Traumatic brain injury, TBI）是全球范围内导致残疾的主要诱因之一，损伤后认知与记忆缺损极为普遍。作为参与学习与记忆的关键脑区，海马体（hippocampus）对创伤性脑损伤尤其易感，而海马齿状回（dentate gyrus）内的细胞功能异常被认为是TBI后认知缺损的主要致病因素。然而，目前对于TBI后亚急性至慢性阶段齿状回内直接发生的转录组变化，我们的认知仍十分有限。

为填补这一研究空白，我们对雄性大鼠接受侧位流体冲击损伤（lateral fluid percussion injury）三周后分离得到的齿状回组织，分别开展了批量RNA测序（bulk RNA sequencing）与单细胞核RNA测序（single nuclei RNA sequencing）。本研究证实，存在持续进展的神经炎症反应，其特征为神经炎症相关基因表达上调，这些基因涉及多条神经炎症通路，并与小胶质细胞（microglia）和星形胶质细胞（astrocyte）的特定亚群密切相关。本研究的R代码已开源于"https://github.com/NgwenyaLab/DeSana_and_Alfawares_2025"。

实验动物为雄性斯普拉格-道利大鼠（Sprague Dawley rats），通过侧位流体冲击损伤构建TBI模型，于损伤三周后实施安乐死。取脑后分离出同侧齿状回组织，分别进行批量RNA测序（每组n=3）与单细胞核RNA测序（每组n=2）。