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 (H(2)S) in the central nervous system. Depending on its concentrations, H(2)S has opposite actions, ranging from neuromodulator to neurotoxic. Nowadays, accurate determination of H(2)S is still an important challenge to understand its biochemistry and functions. In this perspective, this study aims to explore H(2)S 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 H(2)S. 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 H(2)S concentrations from neurological diseases and opens up new perspectives on the potential clinical relevance of H(2)S and its potential therapeutic application.