Enhanced cargo of plasma alpha B crystallin in oligodendrocyte-derived exosomes accompanied by elevated expression of inflammatory factors in the temporal cortex of patients with refractory epilepsy.

PURPOSE: Plasma exosomes have emerged as key mediators of communication between neural cells and the periphery, playing pivotal roles in various neurological diseases. However, their involvement in the pathogenesis of epilepsy remains unclear. This study aimed to investigate the expression of alpha B crystallin (CRYAB) in plasma exosomes and the temporal cortex as a potential contributor to epileptogenesis.

METHODS: The study included 112 participants, comprising patients with refractory medial temporal lobe epilepsy, glioma patients with and without pre-operative epilepsy, and age- and sex-matched healthy controls. Plasma exosomes were isolated from peripheral blood using immuno-co-precipitation and resin antibody techniques. Exosome morphology and size distribution were evaluated using transmission electron microscopy and nanoparticle tracking analysis. Neuron- or glia-derived exosomes were enriched through antibody-based immunoabsorption. Plasma CRYAB levels were quantified using an enzyme-linked immunosorbent assay. CRYAB expression in neurons and glia of the human temporal cortex was evaluated by immunocytochemistry. Western blotting was performed to detect the expression levels of CRYAB and inflammatory cytokines in brain tissue.

RESULTS: Isolated circulating exosomes were confirmed to be partially derived from the central nervous system (CNS), as evidenced by the presence of neuronal and glial markers. CRYAB was highly expressed in exosomes derived from oligodendrocytes. Patients with epilepsy exhibited significantly elevated levels of plasma oligodendrocyte-derived exosomal CRYAB compared to healthy controls. This was paralleled by increased expression of CRYAB in the temporal cortex of patients with epilepsy, indicating CNS origin of the exosomal cargo. A negative correlation between plasma CRYAB levels and oligodendrocyte-derived exosomal CRYAB was observed in both controls and epileptic patients. Furthermore, patients with epilepsy demonstrated significantly higher density of CRYAB immunoreactivity in temporal cortex oligodendrocytes. The temporal cortex of patients with refractory epilepsy exhibited a significant upregulation of CRYAB, concomitant with elevated levels of inflammatory cytokines.

CONCLUSION: The finding that plasma oligodendrocyte-derived exosomal CRYAB is upregulated in patients with epilepsy highlights a potential role of oligodendrocyte-secreted CRYAB in its pathogenesis.