High Translocation of High Mobility Group Box 1 in the Brain Tissue of Patients with Sturge-Weber Syndrome.

Abstract

Purpose: Sturge-Weber syndrome (SWS), a rare congenital neurological and skin disorder, is frequently associated with drug-resistant epilepsy. Translocation of high mobility group box 1 (HMGB1) protein from the nucleus to the cytoplasm or extracellular milieu has been implicated in neuroinflammatory processes contributing to the development of epileptogenesis. This study aimed to explore the expression and distribution of HMGB1 in brain tissue from SWS patients with drug-resistant epilepsy, with the goal of elucidating its potential involvement in the pathogenesis of epilepsy.

Patients and methods: The study enrolled eight patients with drug-resistant epilepsy who underwent hemispherectomy. Brain tissue specimens were obtained and analyzed using immunofluorescence staining to detect HMGB1 distribution in microglia, astrocytes, or different neuronal subtypes. Correlation analyses were performed to investigate the potential relationship between HMGB1 translocation within cells and the clinical characteristics of SWS patients.

Results: In lesional tissues of SWS patients, we observed significantly higher cytoplasmic HMGB1 levels. Meanwhile, HMGB1 was widely distributed in the cytoplasm of microglia and neurons, while in astrocytes, it was primarily localized in the nucleus. This translocation occurred across many neuronal subtypes, including excitatory glutamatergic, inhibitory GABAergic, and cholinergic neurons. The lower proportion of HMGB1-translocated cholinergic neurons was seen compared to the other two neuronal subtypes. Furthermore, no correlation was found between cytoplasmic HMGB1 levels and clinical characteristics of SWS patients.

Conclusion: The results suggest the involvement of HMGB1 in the pathogenesis of drug-resistant epilepsy in SWS patients. Additional research is required to elucidate the precise mechanisms and potential therapeutic targets associated with HMGB1 that underlie the epilepsy linked to SWS.