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Thus, it is essential to understand the mechanism that drives HTN-induced brain pathogenesis for devising novel therapy. This study explored spatial learning, vessels-associated microglia and neuroinflammation during angiotensin II (Ang II) induced HTN with the hypothesis that after HTN induction, endogenous H\n                    <jats:sub>2<\/jats:sub>\n                    S level contributes to neuropathology in HTN. Male Sprague Dawley rats received Ang II (600\u2009ng\/kg\/min) or saline using an implanted osmotic pump, and NaHS (4\u2009mg\/kg), an H\n                    <jats:sub>2<\/jats:sub>\n                    S donor was given intraperitoneally 10 days prior and during Ang II infusion. We employed H\n                    <jats:sub>2<\/jats:sub>\n                    S estimation by amperometric probe, spatial learning was assessed through the Morris water maze task, and synaptic proteins were probed in a synaptosomal fraction of hippocampus homogenate using Western blot. Additionally, rat cytokine array and immunofluorescence were used to screen for chemokine and cytokine, and the endothelium microglial phenotype, respectively. The pretreatment of NaHS attenuated Ang II-induced spatial learning and perturbation of synaptic protein in the hippocampus. It is associated with significant reduction in endothelial activation and microglia pro-inflammatory phenotype in both parenchymal and vessel-associated microglia. Moreover, above observation is accompanied by decreased proinflammatory cytokines and chemokines, such as, TNF-\u03b1, MCP-1, VEGF, and IL-1\u0251, among others. In summary, our data demonstrated that maintenance of H\n                    <jats:sub>2<\/jats:sub>\n                    S level attenuated HTN induced spatial learning deficit by suppressing neuroinflammation and endothelial NOX2 expression. Therefore, reinforcing the role of H\n                    <jats:sub>2<\/jats:sub>\n                    S in alleviating oxidant-induced inflammatory injury and eventually maintaining brain function.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-04178-0","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:35:27Z","timestamp":1781926527000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen sulfide mitigates spatial learning deficits in angiotensin II-Induced hypertension via inhibition of endothelial NOX2 and neuroinflammation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-1653","authenticated-orcid":false,"given":"Gaurav","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamal","family":"Goswami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4066-0823","authenticated-orcid":false,"given":"Manish","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"4178_CR1","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1056\/NEJMsa0903829","volume":"361","author":"AV Chobanian","year":"2009","unstructured":"Chobanian AV. 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