Zhuang Yuan, Liao Xixian, Niu Fei, Li Ming, Yan Yu, He Chuanhang, Wu Xiang, Tian Runfa, Gao Guoyi
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Nat Commun. 2025 May 31;16(1):5082. doi: 10.1038/s41467-025-59856-2.
The mammalian brainstem is particularly vulnerable to mild traumatic brain injury (mTBI), which is associated with prolonged autonomic dysfunction and coma. The spatial cellular connections within the brainstem or the mechanisms underlying its response to injury have been underestimated. Here, we performed single-nucleus RNA sequencing with spatial transcriptome sequencing in both normal and mTBI brainstems in male mice, revealing thirty-five neuron and non-neuron clusters. Typically, we identified subtypes of neurons that co-release multiple neurotransmitters, especially in the sagittal midline of the brainstem. Spatially adjacent neurons sharing similar gene expression patterns. The brainstem's response to mTBI has two features: (1) Oligodendrocytes around the fourth ventricle exhibit widespread disconnection at 1-h post-injury, and (2) Injury-related noradrenergic neurons, particularly in their interaction with neurons located in theIRt and the Sol. These findings provides a reference for further integrative investigations of cellular and circuit functions of brainstem.
哺乳动物的脑干特别容易受到轻度创伤性脑损伤（mTBI）的影响，这种损伤与长期的自主神经功能障碍和昏迷有关。脑干内的空间细胞连接或其对损伤的反应机制一直被低估。在这里，我们对雄性小鼠正常和mTBI脑干进行了单核RNA测序和空间转录组测序，揭示了35个神经元和非神经元簇。通常，我们鉴定出了共同释放多种神经递质的神经元亚型，特别是在脑干的矢状中线。空间上相邻的神经元具有相似的基因表达模式。脑干对mTBI的反应有两个特点：（1）第四脑室周围的少突胶质细胞在损伤后1小时出现广泛的脱失，（2）与损伤相关的去甲肾上腺素能神经元，特别是它们与位于IRt和Sol的神经元的相互作用。这些发现为进一步综合研究脑干的细胞和回路功能提供了参考。
