Investigating Different Forms of Hydrogen Sulfide in Cerebrospinal Fluid of Various Neurological Disorders

Over the past 30 years a considerable amount of data has accumulated on the multifaceted role of hydrogen sulfide (H₂S) in the central nervous system. Depending on its concentrations, H₂S has opposite actions, ranging from neuromodulator to neurotoxic. Nowadays, accurate determination of H₂S is still an important challenge to understand its biochemistry and functions. In this perspective, this study aims to explore H₂S levels in cerebrospinal fluid (CSF), key biofluid for neurological studies, and to assess alleged correlations with neuroinflammatory and neurodegenerative mechanisms. A validated analytical determination combining selective electrochemical detection with ion chromatography was developed to measure free and bound sulfur forms of H₂S. A first cohort of CSF samples (n = 134) was analyzed from patients with inflammatory and demyelinating disorders (acute disseminated encephalomyelitis; multiple sclerosis), chronic neurodegenerative diseases (Alzheimer disease; Parkinson disease), and motor neuron disease (Amyotrophic lateral sclerosis). Given its analytical features, the chromatographic method resulted sensitive, reproducible and robust. We also explored low molecular weight-proteome linked to sulphydration by proteomics analysis on matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). This study is a first clinical report on CSF H₂S concentrations from neurological diseases and opens up new perspectives on the potential clinical relevance of H₂S and its potential therapeutic application.