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

Hydrogen sulfide (H(2)S), 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 H(2)S 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 H(2)S 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 H(2)S. 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 H(2)S concentrations. This review focuses on the neuropathology of high acute H(2)S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H(2)S‐induced neurodegeneration.