Altered Neuroplasticity in Epilepsy is Associated with Neuroinflammation and Oxidative Stress: In vivo Evidence of Brain-Derived Extracellular Vesicles.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.