Figure 2.

A brief and general overview of hydrogen sulfide as a signaling molecule in brain cellular communication. H₂S, a byproduct of mammalian tissues through enzymatic and nonenzymatic pathways, is mainly produced in the brain by astrocytes. Compensatory condition (A): H₂S, is metabolized by astrocytes, mainly via cytosolic enzyme CBS (cystathionine β synthase) and via the 3MST/CAT pathway in the mitochondria. In the early phases of brain injuries (hypoxic conditions, pathological degeneration), H₂S supports the mitochondrial respiratory chain and supports intra-cellular communication by sustaining Ca²⁺ waves while boosting glycolysis and its end product, lactate. Lactate, released by glial cells in the cleft, is captured by the neuron and used as a source of energy. Non-compensatory condition (B): Excessive presence of H₂S (either due to a prolonged exposure or due to levels above the physiological limit) impairs the mitochondrial respiratory chain and leads to a decrease in glycolysis and lactate (as indicated by the red cross), depriving the neurons of their metabolic fuel. Additionally, a non-compensatory condition may well facilitate the astrocytes’ transformation from differentiated to reactive and make them unable to sustain Ca²⁺ waves. Reactive astrocytes have a diminished ability to remove extracellular H₂S, further increasing its concentration in the cleft.