{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:56:09Z","timestamp":1788400569028,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T00:00:00Z","timestamp":1556841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["17-15-01111"],"award-info":[{"award-number":["17-15-01111"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["4.8192.2017\/8.9"],"award-info":[{"award-number":["4.8192.2017\/8.9"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia\/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5\u2032-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg\/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg\/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 \u00b1 0.3 \u03bcM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant\/antiradical IQ-1S activity.<\/jats:p>","DOI":"10.3390\/molecules24091722","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T03:15:46Z","timestamp":1557198946000},"page":"1722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-6586","authenticated-orcid":false,"given":"Mark B.","family":"Plotnikov","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, Tomsk 634028, Russia"},{"name":"National Research Tomsk State University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina A.","family":"Chernysheva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, Tomsk 634028, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg I.","family":"Aliev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, Tomsk 634028, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera I.","family":"Smol\u2019iakova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, Tomsk 634028, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana I.","family":"Fomina","sequence":"additional","affiliation":[{"name":"Department of Medicine Toxicology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, Tomsk 634028, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton N.","family":"Osipenko","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-6548","authenticated-orcid":false,"given":"Victoria S.","family":"Rydchenko","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-0730","authenticated-orcid":false,"given":"Yana J.","family":"Anfinogenova","sequence":"additional","affiliation":[{"name":"Cardiology Research Institute, Tomsk NRMC, Tomsk 634012, Russia"},{"name":"Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-4510","authenticated-orcid":false,"given":"Andrei I.","family":"Khlebnikov","sequence":"additional","affiliation":[{"name":"Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia"},{"name":"Research Institute of Biological Medicine, Altai State University, Barnaul 656049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor A.","family":"Schepetkin","sequence":"additional","affiliation":[{"name":"Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia"},{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy N.","family":"Atochin","sequence":"additional","affiliation":[{"name":"Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia"},{"name":"Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.brainresrev.2006.11.003","article-title":"Molecular targets in cerebral ischemia for developing novel therapeutics","volume":"54","author":"Mehta","year":"2007","journal-title":"Brain Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1002\/j.1460-2075.1996.tb00636.x","article-title":"Selective interaction of JNK protein kinase isoforms with transcription factors","volume":"15","author":"Gupta","year":"1996","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459265","DOI":"10.1155\/2012\/459265","article-title":"Diverse roles of JNK and MKK pathways in the brain","volume":"2012","author":"Yamasaki","year":"2012","journal-title":"J. Signal Transduct."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1460-9568.2005.03857.x","article-title":"Specific pathophysiological functions of JNK isoforms in the brain","volume":"21","author":"Brecht","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/00004647-200007000-00008","article-title":"Alteration of MAP kinase pathways after transient forebrain ischemia","volume":"20","author":"Hu","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.brainres.2013.11.031","article-title":"The protective effect of HET0016 on brain edema and blood-brain barrier dysfunction after cerebral ischemia\/reperfusion","volume":"1544","author":"Liu","year":"2014","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3389\/fphar.2018.00715","article-title":"c-Jun N-terminal kinases (JNKs) in myocardial and cerebral ischemia\/reperfusion injury","volume":"9","author":"Shvedova","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2174\/1568007053005145","article-title":"Targeting the JNK signaling pathway for stroke and Parkinson\u2019s diseases therapy","volume":"4","author":"Kuan","year":"2005","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1124\/mol.111.077446","article-title":"Identification and characterization of a novel class of c-Jun N-terminal kinase inhibitors","volume":"81","author":"Schepetkin","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1517\/13543776.2015.1039984","article-title":"c-Jun N-terminal kinase inhibitors: A patent review (2010\u20132014)","volume":"25","author":"Gehringer","year":"2015","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/sj.bjp.0707574","article-title":"AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon\/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils","volume":"153","author":"Carboni","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.bmcl.2011.12.028","article-title":"Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury","volume":"22","author":"Krenitsky","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/00004647-200206000-00001","article-title":"Role of mitogen- and stress-activated kinases in ishemic injury.","volume":"22","author":"Irving","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1124\/jpet.103.064246","article-title":"AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): A c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties","volume":"310","author":"Carboni","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/sj.jcbfm.9600062","article-title":"Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N-terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway","volume":"25","author":"Gao","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2006.03.086","article-title":"Neuroprotection against ischemic brain injury by SP600125 via suppressing the extrinsic and intrinsic pathways of apoptosis","volume":"1092","author":"Guan","year":"2006","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1021\/jm501212r","article-title":"Inhibitors of c-Jun N-terminal kinases: An update","volume":"58","author":"Koch","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10495-008-0304-8","article-title":"Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke","volume":"14","author":"Yuan","year":"2009","journal-title":"Apoptosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1124\/jpet.114.220251","article-title":"Anti-inflammatory effects and joint protection in collagen-induced arthritis after treatment with IQ-1S, a selective c-Jun N-terminal kinase inhibitor","volume":"353","author":"Schepetkin","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2016.02.033","article-title":"A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice","volume":"618","author":"Atochin","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.neuroscience.2008.03.061","article-title":"Coupling between neuronal nitric oxide synthase and glutamate receptor 6-mediated c-Jun N-terminal kinase signaling pathway via S-nitrosylation contributes to ischemia neuronal death","volume":"155","author":"Yu","year":"2008","journal-title":"Neuroscience"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/jnr.20669","article-title":"Neuroprotective effects of GluR6 antisense oligodeoxynucleotides on transient brain ischemia\/reperfusion-induced neuronal death in rat hippocampal CA1 region","volume":"82","author":"Pei","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1161\/STROKEAHA.108.541128","article-title":"Update of the stroke therapy academic industry roundtable preclinical recommendations","volume":"40","author":"Fisher","year":"2009","journal-title":"Stroke"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.biocel.2015.02.009","article-title":"Mechanical stretch promotes matrix metalloproteinase-2 and prolyl-4-hydroxylase \u03b11 production in human aortic smooth muscle cells via Akt-p38 MAPK-JNK signaling","volume":"62","author":"Liu","year":"2015","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00204-014-1260-4","article-title":"4-Hydroxy-trans-2-nonenal (4-HNE) induces neuronal SH-SY5Y cell death via hampering ATP binding at kinase domain of Akt1","volume":"89","author":"Kashyap","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(07)60154-8","article-title":"Established treatments for acute ischaemic stroke","volume":"369","author":"Khaja","year":"2007","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ginsberg, M.D., and Bogousslavsky, J. (1998). Small-animal models of global and focal cerebral ischemia. Cerebrovascular Disease: Pathophysiology, Diagnosis and Management, Blackwell Science Publisher.","DOI":"10.1016\/B978-012743170-3\/50035-2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1177\/1747493017711814","article-title":"Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group","volume":"12","author":"Corbett","year":"2017","journal-title":"Int. J. Stroke"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/j.1476-5381.2011.01398.x","article-title":"Preclinical stroke research\u2014Advantages and disadvantages of the most common rodent models of focal ischaemia","volume":"164","author":"Macrae","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1093\/brain\/awx126","article-title":"Neuroprotection in stroke: The importance of collaboration and reproducibility","volume":"140","author":"Neuhaus","year":"2017","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nm.3097","article-title":"Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy","volume":"19","author":"Papadakis","year":"2013","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.drudis.2006.06.001","article-title":"Therapeutic strategies for the treatment of stroke","volume":"11","author":"Green","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.clineuro.2009.04.001","article-title":"The complexity of neurobiological processes in acute ischemic stroke","volume":"111","author":"Brouns","year":"2009","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.brainresbull.2017.06.005","article-title":"An improved three-vessel occlusion model of global cerebral ischemia in rats","volume":"132","author":"Atochin","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s10517-012-1600-4","article-title":"A new rat model of reversible global cerebral ischemia","volume":"152","author":"Shcherbak","year":"2012","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.phymed.2016.03.015","article-title":"Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats","volume":"23","author":"Atochin","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2147\/JEP.S63544","article-title":"Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke","volume":"7","author":"Martynov","year":"2015","journal-title":"J. Exp. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369021","DOI":"10.1155\/2015\/369021","article-title":"Luoyutong treatment promotes functional recovery and neuronal plasticity after cerebral ischemia-reperfusion injury in rats","volume":"2015","author":"Wang","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_40","first-page":"1","article-title":"The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats","volume":"7","author":"Yuliani","year":"2018","journal-title":"Nutr. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1476-5381.1992.tb12764.x","article-title":"Long-term changes in gerbil brain neurotransmitter receptors following transient cerebral ischaemia","volume":"107","author":"Araki","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","first-page":"1","article-title":"Rodent models of global cerebral ischemia","volume":"12","author":"Clemens","year":"2001","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.04.010","article-title":"Citicoline for acute ischemic stroke: A systematic review and formal meta-analysis of randomized, double-blind, and placebo-controlled trials","volume":"25","author":"Secades","year":"2016","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0140-6736(12)60813-7","article-title":"Citicoline in the treatment of acute ischaemic stroke: An international, randomised, multicentre, placebo-controlled study (ICTUS trial)","volume":"380","author":"Castillo","year":"2012","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1016\/j.bmc.2010.06.090","article-title":"Lipophilic phenolic antioxidants: Correlation between antioxidant profile, partition coefficients and redox properties","volume":"18","author":"Roleira","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15184","DOI":"10.1073\/pnas.2336254100","article-title":"A critical role of neural-specific JNK3 for ischemic apoptosis","volume":"100","author":"Kuan","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0304-3940(00)01024-7","article-title":"c-Jun N-terminal kinase (JNK) and JNK interacting protein response in rat brain after transient middle cerebral artery occlusion","volume":"284","author":"Hayashi","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00401-002-0661-2","article-title":"Early modifications in the expression of mitogen-activated protein kinase (MAPK\/ERK), stress-activated kinases SAPK\/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia","volume":"105","author":"Ferrer","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/nm911","article-title":"A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia","volume":"9","author":"Borsello","year":"2003","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainres.2005.09.001","article-title":"Activation of c-Jun NH2-terminal kinase 3 is mediated by the GluR6.PSD-95.MLK3 signaling module following cerebral ischemia in rat hippocampus","volume":"1061","author":"Tian","year":"2005","journal-title":"Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejphar.2007.07.040","article-title":"Vasorelaxant activity of some oxime derivatives","volume":"575","author":"Jaros","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0092-8674(00)00116-1","article-title":"Signal transduction by the JNK group of MAP kinases","volume":"103","author":"Davis","year":"2000","journal-title":"Cell"},{"key":"ref_53","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_54","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_55","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.brainres.2014.12.033","article-title":"Inhibition of thioredoxin-1 with siRNA exacerbates apoptosis by activating the ASK1-JNK\/p38 pathway in brain of a stroke model rats","volume":"1599","author":"Wu","year":"2015","journal-title":"Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.freeradbiomed.2005.05.003","article-title":"Antioxidant strategies in the treatment of stroke","volume":"39","author":"Margaill","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0028-3908(01)00019-3","article-title":"Oxidative stress induced-neurodegenerative diseases: The need for antioxidants that penetrate the blood brain barrier","volume":"40","author":"Melamed","year":"2001","journal-title":"Neuropharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/1568007053544156","article-title":"Free radical trapping as a therapeutic approach to neuroprotection in stroke: Experimental and clinical studies with NXY-059 and free radical scavengers","volume":"4","author":"Green","year":"2005","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1161\/01.STR.0000209330.73175.34","article-title":"Toward a multimodal neuroprotective treatment of stroke","volume":"37","author":"Rogalewski","year":"2006","journal-title":"Stroke"},{"key":"ref_60","first-page":"151","article-title":"Biochemistry of ischemic stroke","volume":"92","author":"Barber","year":"2003","journal-title":"Adv. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pollack, G.H., Cameron, I.V., and Wheatly, D.N. (2006). Biological significance of active oxygen-dependent processes in aqueous systems. Water and the Cell, Springer.","DOI":"10.1007\/1-4020-4927-7"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0014-5793(82)80219-6","article-title":"Microsomal lipid peroxidation causes an increase in the order of the membrane lipid domain","volume":"142","author":"Eichenberger","year":"1982","journal-title":"FEBS Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"247","DOI":"10.9734\/IRJPAC\/2012\/2104","article-title":"Reactive secondary sequence oxidative pathology polymer model and antioxidant tests","volume":"2","author":"Petersen","year":"2012","journal-title":"Int. Res. J. Pure Appl. Chem."},{"key":"ref_64","unstructured":"Otto, M. (2000). Analytische Chemie, Zweite, vollst\u00e4ndig \u00fcberarbeitete Auflage, Wiley-VCH Verlag GmbH."},{"key":"ref_65","unstructured":"Folkow, B., and Neil, E. (1971). Circulation, Oxford University Press."},{"key":"ref_66","unstructured":"Chenysheva, G.A., Smol\u2019yakova, V.I., Yanovskaya, E.A., Gurto, R.V., Udut, V.V., and Plotnikov, M.B. Pharmacokinetics of IQ-1S (manuscript in preparation)."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1254\/jphs.FP0050777","article-title":"C-Jun N-terminal kinase contributes to norepinephrine-induced contraction through phosphorylation of caldesmon in rat aortic smooth muscle","volume":"100","author":"Lee","year":"2006","journal-title":"J. Pharmacol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3349\/ymj.2011.52.3.420","article-title":"C-Jun NH2-terminal kinase contributes to dexmedetomidine-induced contraction in isolated rat aortic smooth muscle","volume":"52","author":"Ok","year":"2011","journal-title":"Yonsei Med. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.STR.22.2.162","article-title":"Chronic blood hyperviscosity in subjects with acute stroke, transient ischemic attack, and risk factors for stroke","volume":"22","author":"Coull","year":"1991","journal-title":"Stroke"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3233\/CH-2011-1480","article-title":"Microcirculation and blood rheology in patients with cerebrovascular disorders","volume":"49","author":"Tikhomirova","year":"2011","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_71","first-page":"110","article-title":"Haemorheological disturbances and possibility of their correction in cerebrovascular diseases","volume":"24","author":"Forconi","year":"1999","journal-title":"J. Mal. Vasc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3233\/CH-2011-1498","article-title":"Endothelium and hyperviscosity","volume":"49","author":"Forconi","year":"2011","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fneur.2018.00249","article-title":"Refocusing neuroprotection in cerebral reperfusion era: New challenges and strategies","volume":"9","author":"Xiong","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_74","first-page":"249","article-title":"Endothelin is a potent constrictor of human intracranial arteries and veins","volume":"26","author":"Hardebo","year":"1989","journal-title":"Blood Vessels"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1152\/japplphysiol.00937.2005","article-title":"Endothelial influences on cerebrovascular tone","volume":"100","author":"Andresen","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/01.STR.23.7.1014","article-title":"Increased plasma endothelin-1 in acute ischemic stroke","volume":"23","author":"Ziv","year":"1992","journal-title":"Stroke"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1161\/STROKEAHA.107.495044","article-title":"High serum levels of endothelin-1 predict severe cerebral edema in patients with acute ischemic stroke treated with t-PA","volume":"39","author":"Moldes","year":"2008","journal-title":"Stroke"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1001\/archneur.1977.00500180028006","article-title":"Experimental cerebral infarction effects of pentobarbital in Mongolian gerbils","volume":"34","author":"McGraw","year":"1977","journal-title":"Arch. Neurol."},{"key":"ref_79","unstructured":"Paxinos, G., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, Academic Press."},{"key":"ref_80","first-page":"106","article-title":"The microscopical structure of the hippocampus in the rat","volume":"109","author":"Kubikova","year":"2008","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_81","first-page":"121","article-title":"In vivo lipoperoxidation in der lober nach partieller hepatotektonic","volume":"21","author":"Plazor","year":"1968","journal-title":"Actabiol. Med. Germ."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant determination by the use of a stable free radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11094-009-0294-z","article-title":"Kinetic method for studying the antiradical activity of medicinal plant extracts","volume":"43","author":"Volkov","year":"2009","journal-title":"Pharm. Chem. J."},{"key":"ref_84","first-page":"85","article-title":"Measurement of red cell deformability and whole blood viscosity using laser-diffraction slit rheometer","volume":"16","author":"Shin","year":"2004","journal-title":"Korea-Aust. Rheol. J."},{"key":"ref_85","first-page":"253","article-title":"Transient microfluidic approach to the investigation of erythrocyte aggregation: Comparison and validation of the method","volume":"20","author":"Hou","year":"2008","journal-title":"Korea-Aust. Rheol. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S0008-6363(96)00027-2","article-title":"Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo","volume":"31","author":"Laursen","year":"1996","journal-title":"Cardiovasc. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1722\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:48:55Z","timestamp":1760186935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,3]]},"references-count":86,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["molecules24091722"],"URL":"https:\/\/doi.org\/10.3390\/molecules24091722","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,3]]}}}