{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:33:36Z","timestamp":1791923616118,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060661, 81660151, 81660751"],"award-info":[{"award-number":["82060661, 81660151, 81660751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain ischemia and reperfusion (I\/R) is one of the most severe clinical manifestations of ischemic stroke, placing a significant burden on both individuals and society. The only FDA-approved clinical treatment for ischemic stroke is tissue plasminogen activator (t-PA), which rapidly restores cerebral blood flow but can have severe side effects. The complex pathological process of brain I\/R has been well-established in the past few years, including energy metabolism disorders, cellular acidosis, doubling of the synthesis or release of excitotoxic amino acids, intracellular calcium homeostasis, free radical production, and activation of apoptotic genes. Recently, accumulating evidence has shown that NO may be strongly related to brain I\/R and involved in complex pathological processes. This review focuses on the role of endogenous NO in pathological processes in brain I\/R, including neuronal cell death and blood brain barrier disruption, to explore how NO impacts specific signaling cascades and contributes to brain I\/R injury. Moreover, NO can rapidly react with superoxide to produce peroxynitrite, which may also mediate brain I\/R injury, which is discussed here. Finally, we reveal several therapeutic approaches strongly associated with NO and discuss their potential as a clinical treatment for ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms23084243","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"4243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Roles of Nitric Oxide in Brain Ischemia and Reperfusion"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6168-5686","authenticated-orcid":false,"given":"Yijie","family":"Wang","sequence":"first","affiliation":[{"name":"Experimental Center of Pathogen Biology, College of Medicine, Nanchang University, Nanchang 330047, China"},{"name":"Queen Mary University of London Nanchang Joint Program, Medical College, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-1311","authenticated-orcid":false,"given":"Fenfang","family":"Hong","sequence":"additional","affiliation":[{"name":"Experimental Center of Pathogen Biology, College of Medicine, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344099, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014From mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00234-006-0183-z","article-title":"Reperfusion injury following cerebral ischemia: Pathophysiology, MR imaging, and potential therapies","volume":"49","author":"Pan","year":"2007","journal-title":"Neuroradiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"220","DOI":"10.24272\/j.issn.2095-8137.2020.042","article-title":"The pathological role of ferroptosis in ischemia\/reperfusion-related injury","volume":"41","author":"Yan","year":"2020","journal-title":"Zool. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","article-title":"Reperfusion injury and reactive oxygen species: The evolution of a concept","volume":"6","author":"Granger","year":"2015","journal-title":"Redox Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.freeradbiomed.2019.02.025","article-title":"Neuroprotective strategies following perinatal hypoxia-ischemia: Taking aim at NOS","volume":"142","author":"Albrecht","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","unstructured":"GBD 2015 Neurological Disorders Collaborator Group (2017). Global, regional, and national burden of neurological disorders during 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 16, 877\u2013897."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fnmol.2020.00028","article-title":"Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury","volume":"13","author":"Wu","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/aps.2018.27","article-title":"Targeting RNS\/caveolin-1\/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: Potential application for drug discovery","volume":"39","author":"Chen","year":"2018","journal-title":"Acta Pharm. Sin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11481-014-9525-5","article-title":"Herbal medicines for ischemic stroke: Combating inflammation as therapeutic targets","volume":"9","author":"Gu","year":"2014","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.pbb.2007.04.015","article-title":"Acute ischemic stroke: Overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia","volume":"87","author":"Durukan","year":"2007","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00395-018-0682-1","article-title":"NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2\u03b1","volume":"113","author":"Zhou","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00424-010-0808-2","article-title":"Nitric oxide and oxidative stress in vascular disease","volume":"459","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/aps.2012.82","article-title":"Targeting reactive nitrogen species: A promising therapeutic strategy for cerebral ischemia-reperfusion injury","volume":"34","author":"Chen","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0005-2728(99)00030-4","article-title":"Roles of nitric oxide in brain hypoxia-ischemia","volume":"1411","author":"Almeida","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hao, L., Wei, X., Guo, P., Zhang, G., and Qi, S. (2016). Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia\/Reperfusion-Induced Damage to CA1 Hippocampal Neurons. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071100"},{"key":"ref_16","first-page":"7674","article-title":"Denitrosylation of nNOS induced by cerebral ischemia-reperfusion contributes to nitrosylation of CaMKII and its inhibition of autophosphorylation in hippocampal CA1","volume":"23","author":"Yu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1161\/CIRCRESAHA.111.253419","article-title":"Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles","volume":"110","author":"Terpolilli","year":"2012","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s001090050119","article-title":"Clinical implications of the involvement of tPA in neuronal cell death","volume":"75","author":"Tsirka","year":"1997","journal-title":"J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S1474-4422(16)00114-9","article-title":"Neuroprotection in acute stroke: Targeting excitotoxicity, oxidative and nitrosative stress, and inflammation","volume":"15","author":"Chamorro","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.molmed.2010.12.008","article-title":"Stroke intervention pathways: NMDA receptors and beyond","volume":"17","author":"Lai","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1126\/science.1072873","article-title":"Treatment of ischemic brain damage by perturbing NMDA receptor PSD-95 protein interactions","volume":"298","author":"Aarts","year":"2002","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/nm1210-1376","article-title":"Fashioning drugs for stroke","volume":"16","author":"Lai","year":"2010","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/nm.2245","article-title":"Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95","volume":"16","author":"Zhou","year":"2010","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1074\/jbc.M111.227124","article-title":"S-nitrosylation of mixed lineage kinase 3 contributes to its activation after cerebral ischemia","volume":"287","author":"Hu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cellsig.2018.11.023","article-title":"Cleavage of arrestin-3 by caspases attenuates cell death by precluding arrestin-dependent JNK activation","volume":"54","author":"Kook","year":"2019","journal-title":"Cell. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuroscience.2012.10.055","article-title":"Endogenous nitric oxide induces activation of apoptosis signal-regulating kinase 1 via S-nitrosylation in rat hippocampus during cerebral ischemia-reperfusion","volume":"229","author":"Liu","year":"2013","journal-title":"Neuroscience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1111\/j.1471-4159.2008.05531.x","article-title":"Exogenous nitric oxide negatively regulates c-Jun N-terminal kinase activation via inhibiting endogenous NO-induced S-nitrosylation during cerebral ischemia and reperfusion in rat hippocampus","volume":"106","author":"Pei","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2990.2012.01284.x","article-title":"Exogenous nitric oxide negatively regulates the S-nitrosylation p38 mitogen-activated protein kinase activation during cerebral ischaemia and reperfusion","volume":"39","author":"Qi","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuron.2019.05.033","article-title":"CaM Kinase: Still Inspiring at 40","volume":"103","author":"Bayer","year":"2019","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1146\/annurev.biochem.71.110601.135410","article-title":"Neuronal CA2+\/calmodulin-dependent protein kinase II: The role of structure and autoregulation in cellular function","volume":"71","author":"Hudmon","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_31","unstructured":"(2004). Brain ischemia induces serine phosphorylation of neuronal nitric oxide synthase by Ca~(2+)\/calmodulin-dependent protein kinase II in rat hippocampus. Acta Pharmacol. Sin., 25, 617\u2013622."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11010-012-1280-4","article-title":"S-nitrosylation of c-Src via NMDAR-nNOS module promotes c-Src activation and NR2A phosphorylation in cerebral ischemia\/reperfusion","volume":"365","author":"Tang","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1161\/STROKEAHA.110.608257","article-title":"Blood-brain barrier breakdown in acute and chronic cerebrovascular disease","volume":"42","author":"Yang","year":"2011","journal-title":"Stroke"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1161\/01.STR.0000126044.83777.f4","article-title":"Reperfusion-induced oxidative\/nitrative injury to neurovascular unit after focal cerebral ischemia","volume":"35","author":"Can","year":"2004","journal-title":"Stroke"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s11011-019-00419-y","article-title":"Magnesium sulfate protects blood\u2013brain barrier integrity and reduces brain edema after acute ischemic stroke in rats","volume":"34","author":"Shadman","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/jcbfm.2013.203","article-title":"Hemorrhagic transformation after ischemic stroke in animals and humans","volume":"34","author":"Jickling","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.neuron.2014.03.003","article-title":"Stepwise recruitment of transcellular and paracellular pathways underlies blood\u2013brain barrier breakdown in stroke","volume":"82","author":"Knowland","year":"2014","journal-title":"Neuron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nm.4309","article-title":"Gpr124 is essential for blood-brain barrier integrity in central nervous system disease","volume":"23","author":"Chang","year":"2017","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1160\/TH14-01-0007","article-title":"Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischemic stroke","volume":"112","author":"Lenglet","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1471-4159.2011.07542.x","article-title":"Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury","volume":"120","author":"Gu","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.2741\/222","article-title":"Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood\u2013brain barrier permeability","volume":"3","author":"Gu","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s10571-011-9711-4","article-title":"Nitric oxide contributes to hypoxia-reoxygenation-induced P-glycoprotein expression in rat brain endothelial cells","volume":"31","author":"Robertson","year":"2011","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1021\/cb800279q","article-title":"Chemical biology of peroxynitrite: Kinetics, diffusion, and radicals","volume":"4","author":"Radi","year":"2009","journal-title":"ACS Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/acs.chemrev.7b00568","article-title":"Biochemistry of Peroxynitrite and Protein Tyrosine Nitration","volume":"118","author":"Campolo","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.freeradbiomed.2021.01.049","article-title":"Identification and relative quantification of 3-nitrotyrosine residues in fibrinogen nitrated in vitro and fibrinogen from ischemic stroke patient plasma using LC-MS\/MS","volume":"165","author":"Medeiros","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.1007\/s12035-017-0859-x","article-title":"Inhibition of Peroxynitrite-Induced Mitophagy Activation Attenuates Cerebral Ischemia-Reperfusion Injury","volume":"55","author":"Feng","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"826143","DOI":"10.1155\/2013\/826143","article-title":"Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death","volume":"2013","author":"Tajes","year":"2013","journal-title":"Oxid Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/cns.12406","article-title":"Peroxynitrite Decomposition Catalyst Reduces Delayed Thrombolysis-induced Hemorrhagic Transformation in Ischemia-reperfused Rat Brains","volume":"21","author":"Chen","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/cr.2013.169","article-title":"Historical landmarks of autophagy research","volume":"24","author":"Ohsumi","year":"2014","journal-title":"Cell Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/ncb2788","article-title":"Emerging regulation and functions of autophagy","volume":"15","author":"Boya","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.bbamcr.2009.03.002","article-title":"Mitophagy","volume":"1793","author":"Tolkovsky","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R170","DOI":"10.1016\/j.cub.2018.01.004","article-title":"Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance","volume":"28","author":"Pickles","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"608610","DOI":"10.3389\/fneur.2020.608610","article-title":"The Role of Mitophagy in Ischemic Stroke","volume":"11","author":"Shao","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/cns.12325","article-title":"BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke","volume":"20","author":"Shi","year":"2014","journal-title":"CNS Neurosci. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1080\/15548627.2017.1357792","article-title":"BNIP3L\/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2","volume":"13","author":"Yuan","year":"2017","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bbrc.2014.01.032","article-title":"Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke","volume":"444","author":"Li","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/jpi.12337","article-title":"Melatonin attenuates traumatic brain injury-induced inflammation: A possible role for mitophagy","volume":"61","author":"Lin","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.freeradbiomed.2020.06.034","article-title":"Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation","volume":"160","author":"Zhang","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/14728222.2017.1281250","article-title":"Reactive nitrogen species as therapeutic targets for autophagy: Implication for ischemic stroke","volume":"21","author":"Feng","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.brainresbull.2018.06.018","article-title":"Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1\/Parkin\/p62 signaling pathway","volume":"142","author":"Lan","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s12975-015-0444-4","article-title":"Extending the Time Window for Endovascular and Pharmacological Reperfusion","volume":"7","author":"Henninger","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s12975-017-0598-3","article-title":"Baicalin Attenuates Blood-Brain Barrier Disruption and Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke Rats with Delayed t-PA Treatment: Involvement of ONOO-MMP-9 Pathway","volume":"9","author":"Chen","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s12975-019-00772-1","article-title":"Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling","volume":"11","author":"Chen","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s12974-018-1267-5","article-title":"Cell permeable HMGB1-binding heptamer peptide ameliorates neurovascular complications associated with thrombolytic therapy in rats with transient ischemic stroke","volume":"15","author":"Li","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1113\/EP087122","article-title":"Ischaemic and hypoxic conditioning: Potential for protection of vital organs","volume":"104","author":"Sprick","year":"2019","journal-title":"Exp. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.brainres.2016.01.008","article-title":"Ischemic preconditioning protects the brain against injury via inhibiting CaMKII-nNOS signaling pathway","volume":"1634","author":"Wang","year":"2016","journal-title":"Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.niox.2019.12.004","article-title":"DDAH-1 via HIF-1 target genes improves cerebral ischemic tolerance after hypoxic preconditioning and middle cerebral artery occlusion-reperfusion","volume":"95","author":"Zhao","year":"2020","journal-title":"Nitric Oxide"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11481-007-9089-8","article-title":"The protective effect of ischemic postconditioning against ischemic injury: From the heart to the brain","volume":"2","author":"Zhao","year":"2007","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.niox.2014.02.002","article-title":"The dynamic detection of NO during the ischemic postconditioning against global cerebral ischemia\/reperfusion injury","volume":"38","author":"Liu","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.brainres.2009.07.029","article-title":"Limb remote ischemic postconditioning protects against focal ischemia in rats","volume":"1288","author":"Ren","year":"2009","journal-title":"Brain Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.brainres.2012.01.033","article-title":"Remote ischemic postconditioning protects the brain from global cerebral ischemia\/reperfusion injury by up-regulating endothelial nitric oxide synthase through the PI3K\/Akt pathway","volume":"1445","author":"Peng","year":"2012","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Leger, P.L., Bonnin, P., Nguyen, T., Renolleau, S., Baud, O., and Charriaut-Marlangue, C. (2012). Ischemic postconditioning fails to protect against neonatal cerebral stroke. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049695"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.3748\/wjg.v16.i48.6079","article-title":"Role of nitric oxide in hepatic ischemia-reperfusion injury","volume":"16","author":"Siriussawakul","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/bph.14512","article-title":"Inhaled nitric oxide","volume":"176","author":"Yu","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.niox.2019.12.001","article-title":"Inhaled nitric oxide use in neonates: Balancing what is evidence-based and what is physiologically sound","volume":"95","author":"Sherlock","year":"2020","journal-title":"Nitric Oxide"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1016\/j.bja.2020.10.011","article-title":"Inhaled nitric oxide minimally improves oxygenation in COVID-19 related acute respiratory distress syndrome","volume":"126","author":"Longobardo","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.brainres.2013.02.031","article-title":"Neuroprotection by inhaled nitric oxide in a murine stroke model is concentration and duration dependent","volume":"1507","author":"Li","year":"2013","journal-title":"Brain Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1161\/STROKEAHA.112.664243","article-title":"Inhaled nitric oxide reduces brain damage by collateral recruitment in a neonatal stroke model","volume":"43","author":"Christiane","year":"2012","journal-title":"Stroke"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s11064-014-1485-x","article-title":"Tetramethylpyrazine analogue CXC195 ameliorates cerebral ischemia-reperfusion injury by regulating endothelial nitric oxide synthase phosphorylation via PI3K\/Akt signaling","volume":"40","author":"Yan","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejphar.2019.03.015","article-title":"Vitexin protects against ischemia\/reperfusion-induced brain endothelial permeability","volume":"853","author":"Cui","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.bbrc.2017.03.131","article-title":"Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms","volume":"486","author":"Lee","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.brainres.2012.11.004","article-title":"Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction","volume":"1491","author":"Hu","year":"2013","journal-title":"Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/8\/4243\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:52:07Z","timestamp":1760136727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/8\/4243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,11]]},"references-count":84,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23084243"],"URL":"https:\/\/doi.org\/10.3390\/ijms23084243","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,11]]}}}