创伤性脑损伤
海马结构
神经干细胞
诱导多能干细胞
细胞外小泡
干细胞
神经科学
衰老
认知功能衰退
海马体
细胞生物学
认知
医学
转录组
生物
氧化应激
细胞外
认知缺陷
心理学
间充质干细胞
下调和上调
衰老的大脑
祖细胞
突触小泡
胞外囊泡
细胞
生物信息学
作者
Tiange Chen,Qian Zhang,Liyang Zhang,Yuejie Ai,Ziyang Chen,Jiacheng Liu,Jiacheng Liu,Ganzhi Liu,Xin Chen,Tao Xu,Yuguo Xia,Jinfang Liu,Jinfang Liu
出处
期刊:ACS Nano
[American Chemical Society]
日期:2025-10-23
卷期号:19 (43): 37783-37801
被引量:1
标识
DOI:10.1021/acsnano.5c10672
摘要
Hippocampal neural stem cells (NSCs) have attracted significant attention due to their essential role in maintaining cognitive functions, such as memory and spatial orientation through neurogenesis. Cognitive impairment is a common and debilitating complication of traumatic brain injury (TBI), yet its underlying mechanisms remain poorly understood and effective clinical interventions are lacking. In this study, we observed persistent cognitive deficits in a mouse model of TBI, a phenomenon that has been widely documented in previous studies, and importantly, we found that these impairments were closely associated with increased hippocampal NSCs (H-NSCs) senescence. To investigate the cause of NSCs' senescence, we analyzed cerebrospinal fluid samples from TBI patients and hippocampal tissues from TBI mice and identified persistently elevated levels of IL-1β post TBI. In vitro, IL-1β successfully induced NSCs' senescence and suppressed neurogenesis. Induced pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) reversed IL-1β-induced senescence and restored neurogenic potential in H-NSCs. In vivo, iPSC-sEVs alleviated cognitive deficits and H-NSC senescence after TBI. Integrated proteomic and NSC cell transcriptomic analyses revealed that the β-catenin/ID2/CDKN2B (p15INK4b) signaling axis plays a critical role in regulating H-NSC senescence, which was further validated through inhibitor experiments. In summary, our findings demonstrate that iPSC-sEVs attenuate NSC senescence and improve cognitive function following TBI via modulation of the β-catenin/ID2/CDKN2B (p15INK4b) axis.
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