Bu Zhang, Zhou Yuqian, Xu Feng, Xu Shan
Department of Emergency Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Soochow University Campus Hospital, Soochow University, Suzhou, Jiangsu, China.
Brain Behav. 2025 May;15(5):e70428. doi: 10.1002/brb3.70428.
After traumatic brain injury (TBI), ischemia and hypoxia of brain tissue, glucose undergoes anaerobic fermentation, leading to a large accumulation of lactic acid. Our aim was to explore the role of lactate metabolism in brain cells after TBI.
In scRNA-seq dataset, 10-week-old male C57BL/6 J mice were randomized to undergo mild fluid percussion injury or sham surgery, and we analyzed frontal cortex tissue during the acute (24 h) and subacute (7 days) phases of TBI at single-cell resolution. Cell cycle phases were evaluated, and principal component analysis was performed. Cell populations were identified and visualized using the UMAP downscaling technique. Differentially expressed genes (DEGs) were analyzed using the "FindAllMarkers" algorithm. In addition, the set of genes related to lactate metabolism was evaluated using the AUCell score. GO and KEGG enrichment analyses were performed to investigate the functional pathways of DEGs in astrocytes in the acute and subacute phases of TBI.
A total of 13 cell populations were distinguished, including neurons, astrocytes, and oligodendrocyte progenitors. The number of neurons, astrocytes, and endothelial cells was reduced in the TBI group compared with the sham group. During the acute phase of TBI, enhanced interactions between brain-associated cells, especially astrocytes and oligodendrocyte precursor cells, were observed. Several signaling pathways, including EGF, CSF, MIF inflammatory factors as well as PSAP and PTN neurotrophic factor signaling were significantly enhanced after TBI. Lactate metabolism scores were elevated in the TBI group, especially in astrocytes. During the subacute phase, the frequency of intercellular communication increased but its intensity decreased. Astrocytes and oligodendrocyte precursor cells remained at high levels during both phases. PSAP signaling was closely associated with the subacute phase of TBI. Subsequently, NADH:ubiquinone oxidoreductase subunit B9 (Ndufb9) and cytochrome c oxidase subunit 8A (Cox8a) were identified as key players in lactate metabolism associated with TBI. Ndufb9 and Cox8a showed a consistent upward trend in brain tissue following TBI with transcriptomic data.
Lactate metabolism genes play an important role in TBI. These findings provide new insights into the cellular and molecular mechanisms following TBI.
创伤性脑损伤（TBI）后，脑组织缺血缺氧，葡萄糖进行无氧酵解，导致乳酸大量蓄积。我们的目的是探讨TBI后脑细胞中乳酸代谢的作用。
在单细胞RNA测序（scRNA-seq）数据集中，将10周龄雄性C57BL/6 J小鼠随机分为轻度液压冲击伤组或假手术组，并在TBI的急性期（24小时）和亚急性期（7天）以单细胞分辨率分析额叶皮质组织。评估细胞周期阶段，并进行主成分分析。使用UMAP降维技术识别并可视化细胞群体。使用“FindAllMarkers”算法分析差异表达基因（DEG）。此外，使用AUCell评分评估与乳酸代谢相关的基因集。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，以研究TBI急性期和亚急性期星形胶质细胞中DEG的功能途径。
共区分出13种细胞群体，包括神经元、星形胶质细胞和少突胶质细胞前体细胞。与假手术组相比，TBI组的神经元、星形胶质细胞和内皮细胞数量减少。在TBI急性期，观察到脑相关细胞之间尤其是星形胶质细胞和少突胶质细胞前体细胞之间的相互作用增强。TBI后，包括表皮生长因子（EGF）、集落刺激因子（CSF）、巨噬细胞移动抑制因子（MIF）等炎症因子以及前列腺素酸性磷酸酶（PSAP）和多效生长因子（PTN）神经营养因子信号等多种信号通路显著增强。TBI组的乳酸代谢评分升高，尤其是在星形胶质细胞中。在亚急性期，细胞间通讯频率增加但其强度降低。星形胶质细胞和少突胶质细胞前体细胞在两个阶段均保持高水平。PSAP信号与TBI亚急性期密切相关。随后，烟酰胺腺嘌呤二核苷酸（NADH）：泛醌氧化还原酶亚基B9（Ndufb9）和细胞色素c氧化酶亚基8A（Cox8a）被确定为与TBI相关的乳酸代谢中的关键因子。Ndufb9和Cox8a在TBI后的脑组织中与转录组数据呈现一致的上升趋势。
乳酸代谢基因在TBI中起重要作用。这些发现为TBI后的细胞和分子机制提供了新的见解。
