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Sodium hydrogen sulfide (NaHS), a known donor of H<jats:sub>2<\/jats:sub>S, is beneficial in various biological processes involving aging and diseases, including injury. It is neuroprotective against oxidative stress, neuroinflammation, and other secondary injury processes. However, the NaHS\u2010H<jats:sub>2<\/jats:sub>S system has not been investigated as a regulator of injury\u2010mediated synaptic plasticity proteins and the underlying mechanisms after TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach<\/jats:title><jats:p>We developed a model of TBI in Swiss albino mice to study the effects of exogenous H<jats:sub>2<\/jats:sub>S, administered as NaHS. We assessed cognitive function (Barnes maze and novel object recognition) and motor function (rotarod). Brain tissue was analysed with ELISA, qRT\u2010PCR, immunoblotting, Golgi\u2010cox staining, and immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>NaHS administration restored the injury\u2010caused decline in H<jats:sub>2<\/jats:sub>S levels. Injury\u2010mediated oxidative stress parameters were improved following NaHS. It down\u2010regulated TBI biomarkers, ameliorated the synaptic marker proteins, and improved cognitive and motor deficits. These changes were accompanied by enhanced dendritic arborization and spine number. Restoration of <jats:italic>N<\/jats:italic>\u2010methyl D\u2010aspartate receptor subunits and diminished glutamate and calcium levels, along with marked changes in microtubule\u2010associated protein 2 A and calcium\/calmodulin\u2010dependent protein kinase II, formed the basis of the underlying mechanism(s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings suggest that NaHS could have therapeutic activity against TBI, as it ameliorated cognitive and motor deficits caused by changes in synaptic plasticity proteins and dendritic arborisation, in our model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17386","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T05:09:27Z","timestamp":1732079367000},"page":"1183-1205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NaHS alters synaptic plasticity proteins and enhances dendritic 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