Distinct Pharmacological Profiles of Monosulfide and Trisulfide in an Experimental Model of Intracerebral Hemorrhage in Mice

Hydrogen sulfide and polysulfides are increasingly recognized as bioactive signaling molecules to produce various actions and regulate (patho)physiological processes. Here we examined the effects of sodium sulfide (Na2S) and sodium trisulfide (Na2S3) on an experimental model of intracerebral hemorrhage (ICH) in mice. Na2S or Na2S3 (25 µmol/kg, intraperitoneally (i.p.)) was administered 30 min before ICH induction by intrastriatal injection of collagenase. We found that Na2S significantly ameliorated sensorimotor functions of mice after ICH. Histopathological examinations revealed that Na2S inhibited neuron loss in the striatum, prevented axon degeneration in the internal capsule, and ameliorated axonal transport dysfunction in the striatum and the cerebral cortex where the edge of hematoma was located. Although Na2S did not suppress accumulation of activated microglia/macrophages in the peri-hematoma region, it suppressed ICH-induced upregulation of inflammatory mediators such as C-X-C motif ligand 2. On the other hand, Na2S3 did not ameliorate ICH-induced sensorimotor dysfunction. Although the effect of Na2S3 on several parameters such as axon degeneration and axonal transport dysfunction was comparable to that of Na2S, Na2S3 did not significantly inhibit neuron loss and upregulation of inflammatory mediators. These results suggest that the regulation of multiple pathological events is involved in the effect of Na2S leading to amelioration of neurological symptoms associated with ICH.