NaHS replenishes hydrogen sulfide levels and rescues myelination defects through NRF2 signaling and iron homeostasis after traumatic brain injury in Swiss albino male mice.

Traumatic brain injury (TBI) profoundly affects individuals, driven by its multifaceted pathology. TBI is a leading cause of neurological disability globally, necessitating novel therapeutic approaches. TBI induces axonal damage, resulting in demyelination. This is marked by the loss of the myelin sheath and oligodendrocyte dysfunctions. The disrupted myelin sheath leads to abnormal neural connectivity, contributing to behavioral outcomes. Recent studies explored the pharmacological treatments that enhance myelination in demyelinating pathological states. Sodium hydrogen sulfide (NaHS), an H2S donor known for its therapeutic benefits in various TBI models, has yet to be investigated for its role in enhancing myelination. To investigate the therapeutic potential of NaHS, a mouse model of TBI was employed. The findings were established by various behavioral tasks. H2S levels were estimated by an AzMC probe, different oligodendrocyte markers were quantitatively analyzed using immunofluorescence, and the iron regulatory and myelin proteins were measured by immunoblotting. The results obtained suggested that NaHS treatment restores the H2S levels and ameliorates the anxiety and depressive symptoms. Moreover, NaHS treatment reduces oxidative stress and enhances antioxidant defense through the activation of NRF2/KEAP1-HO-1 signaling. Additionally, it increases the number of total and mature oligodendrocytes, restores iron regulatory proteins, and upregulates the different myelin proteins, thereby enhancing myelination. These findings suggest that NaHS not only restores redox balance and alleviates behavioral deficits but also holds significant promise for addressing oxidative stress and myelination deficits, offering a novel therapeutic avenue for TBI treatment.