Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research

Hydrogen sulfide (H₂S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H₂S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H₂S is known to cause brain damage, leading to neurodegeneration and long-term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H₂S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H₂S concentrations. This review focuses on the neuropathology of high acute H₂S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H₂S-induced neurodegeneration.