近日，美国波士顿大学Jonathan D. Cherry及其课题组的研究显示，反复的头部创伤会导致年轻运动员的神经元丢失和炎症。该研究于2025年9月17日发表于国际一流学术期刊《自然》杂志上。

在这里，研究小组观察到CTE p-tau病理发病前的多细胞反应与RHI暴露的年轻人（小于51岁）的年数相关，其中大多数人踢美式足球。利用来自8个对照个体、9个RHI暴露个体和11个低期CTE个体的组织的单核RNA测序，小组在RHI暴露的个体中发现了表达SPP1的炎性小胶质细胞、血管生成细胞和炎症内皮细胞、星形细胞增生和突触基因表达改变。该课题组人员还观察到与p-tau病理无关的皮质沟层2/3神经元的显著丢失。最后，研究团队确定TGFβ1是介导小胶质细胞-内皮细胞串扰的潜在信号。这些结果提供了有力的证据，证明多年的RHI足以诱导持续的细胞改变，这可能是p-tau沉积的基础，并有助于解释年轻前接触性运动运动员的早期发病机制。

此外，这些数据确定了对RHI的特定细胞反应，可能指导未来CTE诊断和治疗策略的确定。

据介绍，身体接触运动引起的重复性头部撞击（RHIs）是慢性创伤性脑病（CTE）的最大危险因素。目前，CTE只能在死亡后诊断，而触发初始过度磷酸化tau（p-tau）沉积的事件仍不清楚。此外，年轻人的症状不能完全用p-tau沉积的程度来解释，严重阻碍了治疗干预。

附：英文原文

Title: Repeated head trauma causes neuron loss and inflammation in young athletes

Author: Butler, Morgane L. M. D., Pervaiz, Nida, Breen, Kerry, Calderazzo, Samantha, Ypsilantis, Petra, Wang, Yichen, Breda, Julia Cammasola, Mazzilli, Sarah, Nicks, Raymond, Spurlock, Elizabeth, Hefti, Marco M., Fiock, Kimberly L., Huber, Bertrand R., Alvarez, Victor E., Stein, Thor D., Campbell, Joshua D., McKee, Ann C., Cherry, Jonathan D.

Issue&Volume: 2025-09-17

Abstract: Repetitive head impacts (RHIs) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE)1,2,3,4. Currently, CTE can only be diagnosed after death and the events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear2. Furthermore, the symptoms endorsed by young individuals are not fully explained by the extent of p-tau deposition2, severely hampering therapeutic interventions. Here we observed a multicellular response prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure in young people (less than 51 years of age) with RHI exposure, the majority of whom played American football. Leveraging single-nucleus RNA sequencing of tissue from 8 control individuals, 9 RHI-exposed individuals and 11 individuals with low-stage CTE, we identify SPP1-expressing inflammatory microglia, angiogenic and inflamed endothelial cells, astrocytosis and altered synaptic gene expression in those exposed to RHI. We also observe a significant loss of cortical sulcus layer 2/3 neurons independent of p-tau pathology. Finally, we identify TGFβ1 as a potential signal that mediates microglia–endothelial cell cross talk. These results provide robust evidence that multiple years of RHI is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early pathogenesis in young former contact sport athletes. Furthermore, these data identify specific cellular responses to RHI that may direct future identification of diagnostic and therapeutic strategies for CTE.

DOI: 10.1038/s41586-025-09534-6

Source: https://www.nature.com/articles/s41586-025-09534-6