Wang Shun, Zhang Haiju, Li Ruiling, Liu Zhongchun, Xiang Dan
Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Int J Nanomedicine. 2025 Jun 4;20:7185-7197. doi: 10.2147/IJN.S514559. eCollection 2025.
Recurrent seizures lead to self-reconstruction of the central nervous system, which is termed the neuroplasticity of epilepsy. While preclinical studies implicate neuroinflammation and oxidative stress in epilepsy-associated neuroplasticity, in vivo molecular-level evidence in humans is lacking.
We used astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) as brain-derived biomarkers to explore biomarkers of neuroplasticity, neuroinflammation, and oxidative stress. A total of 50 patients in the epilepsy group (EP) and 25 matched healthy controls (HC) were recruited for this study. Plasma ADEVs and NDEVs were isolated and confirmed, and the levels of the EV marker CD81, the neuroplasticity marker brain-derived neurotrophic factor (BDNF), and the neuroinflammation marker tumor necrosis factor α (TNF-α) in ADEVs, as well as the markers of oxidative stress, superoxide dismutase 1 (SOD1) and malondialdehyde (MDA), in NDEVs were measured.
BDNF levels in ADEVs and SOD1 levels in NDEVs from EP were significantly lower than those in HC, whereas TNF-α levels in ADEVs and MDA levels in NDEVs were significantly increased, and the results remained stable after normalization by CD81. Spearman correlation analysis revealed that BDNF levels in ADEVs were negatively correlated with TNF-α levels in ADEVs and MDA levels in NDEVs and positively correlated with SOD1 levels in NDEVs.
The innovative use of ADEVs and NDEVs as brain-derived biomarkers in this study provides in vivo evidence that epilepsy may result in impaired neuroplasticity and may be associated with increased neuroinflammation and oxidative stress.
癫痫反复发作会导致中枢神经系统的自我重建，这被称为癫痫的神经可塑性。虽然临床前研究表明神经炎症和氧化应激与癫痫相关的神经可塑性有关，但缺乏人体体内分子水平的证据。
我们使用星形胶质细胞衍生的细胞外囊泡（ADEVs）和神经元衍生的细胞外囊泡（NDEVs）作为脑源性生物标志物，以探索神经可塑性、神经炎症和氧化应激的生物标志物。本研究共招募了50例癫痫组（EP）患者和25例匹配的健康对照（HC）。分离并确认血浆中的ADEVs和NDEVs，测量ADEVs中细胞外囊泡标志物CD81、神经可塑性标志物脑源性神经营养因子（BDNF）和神经炎症标志物肿瘤坏死因子α（TNF-α）的水平，以及NDEVs中氧化应激标志物超氧化物歧化酶1（SOD1）和丙二醛（MDA）的水平。
EP组ADEVs中的BDNF水平和NDEVs中的SOD1水平显著低于HC组，而ADEVs中的TNF-α水平和NDEVs中的MDA水平显著升高，经CD81标准化后结果保持稳定。Spearman相关性分析显示，ADEVs中的BDNF水平与ADEVs中的TNF-α水平和NDEVs中的MDA水平呈负相关，与NDEVs中的SOD1水平呈正相关。
本研究创新性地将ADEVs和NDEVs用作脑源性生物标志物，提供了体内证据，表明癫痫可能导致神经可塑性受损，并可能与神经炎症和氧化应激增加有关。
