{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:25:50Z","timestamp":1791473150387,"version":"4.3.4"},"reference-count":236,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ7\/02699"],"award-info":[{"award-number":["2019\/33\/B\/NZ7\/02699"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO\u2022), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive oxygen and nitrogen species (ROS\/RNS) in neurons due to NO\u2022 synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) and HIF-1\u03b1-dependent genes activated in reactive astrocytes play essential roles in this process. The review summarizes the roles of NO\u2022-dependent pathways in the early and late aftermath of stroke and treatments based on the stimulation or inhibition of particular NO\u2022 synthases and the stabilization of HIF-1\u03b1 activity.<\/jats:p>","DOI":"10.3390\/biom11081097","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T04:19:30Z","timestamp":1627273170000},"page":"1097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia"],"prefix":"10.3390","volume":"11","author":[{"given":"Joanna M","family":"Wiero\u0144ska","sequence":"first","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna Street 12, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-573X","authenticated-orcid":false,"given":"Paulina","family":"Cie\u015blik","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna Street 12, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Kalinowski","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics\u2014Biobank Fahrenheit BBMRI.pl, Medical University of Gdansk, Debinki Street 7, 80-211 Gdansk, Poland"},{"name":"Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7, 80-211 Gdansk, Poland"},{"name":"BioTechMed Center\/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Narutowicza 11\/12, 80-223 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). 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