{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:58:38Z","timestamp":1780934318375,"version":"3.54.1"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T00:00:00Z","timestamp":1532649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Russian Science Foundation","award":["14-15-00147"],"award-info":[{"award-number":["14-15-00147"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neonatal hypoxia\u2013ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia\u2013ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia\u2013ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia\u2013ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia\u2013ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.<\/jats:p>","DOI":"10.3390\/molecules23081871","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T12:20:03Z","timestamp":1532694003000},"page":"1871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic\u2013Ischemic Brain Injury"],"prefix":"10.3390","volume":"23","author":[{"given":"Denis N.","family":"Silachev","sequence":"first","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor Y.","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina B.","family":"Pevzner","sequence":"additional","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljubava D.","family":"Zorova","sequence":"additional","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia V.","family":"Balakireva","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-2484","authenticated-orcid":false,"given":"Mikhail V.","family":"Gulyaev","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Prospekt, house 31-5, 117192 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury A.","family":"Pirogov","sequence":"additional","affiliation":[{"name":"Faculty of Physics, Lomonosov Moscow State University, Leninskye gory, house 1, building 2, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir P.","family":"Skulachev","sequence":"additional","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry B.","family":"Zorov","sequence":"additional","affiliation":[{"name":"A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0140-6736(14)61698-6","article-title":"Global, regional, and national causes of child mortality in 2000\u201313, with projections to inform post-2015 priorities: An updated systematic analysis","volume":"385","author":"Liu","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jpeds.2015.02.056","article-title":"Neuroprotection for Perinatal Hypoxic Ischemic Encephalopathy in Low- and Middle-Income Countries","volume":"167","author":"Tagin","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1053\/j.nainr.2011.07.004","article-title":"Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments","volume":"11","author":"Allen","year":"2011","journal-title":"Newborn Infant Nurs. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhu, P., Fujino, M., Zhuang, J., Guo, H., Sheikh, I., Zhao, L., and Li, X.-K. (2016). Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122078"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.hlc.2014.05.022","article-title":"The mitochondrion as a key regulator of ischaemic tolerance and injury","volume":"23","author":"Silachev","year":"2014","journal-title":"Heart Lung Circ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1056\/NEJMra041996","article-title":"Neonatal brain injury","volume":"351","author":"Ferriero","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.freeradbiomed.2005.03.035","article-title":"Free radicals as triggers of brain edema formation after stroke","volume":"39","author":"Heo","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"404","DOI":"10.2174\/092986708783497337","article-title":"Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging","volume":"15","author":"Slemmer","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0898-6568(98)00037-0","article-title":"Redox regulation of cellular signalling","volume":"11","author":"Kamata","year":"1999","journal-title":"Cell. Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0006-2952(02)01137-1","article-title":"Antioxidants and oxidants regulated signal transduction pathways","volume":"64","author":"Owuor","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"542976","DOI":"10.1155\/2012\/542976","article-title":"Hypoxic-ischemic injury in the developing brain: The role of reactive oxygen species originating in mitochondria","volume":"2012","author":"Ten","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1006\/abbi.1995.1436","article-title":"Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel thiol reagent targeted to the mitochondrial matrix","volume":"322","author":"Burns","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1046\/j.1432-1327.1999.00543.x","article-title":"Selective targeting of an antioxidant to mitochondria","volume":"263","author":"Smith","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1134\/S0006297908120018","article-title":"Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: Synthesis and in vitro studies","volume":"73","author":"Antonenko","year":"2008","journal-title":"Biochem. Mosc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14487","DOI":"10.3390\/molecules200814487","article-title":"Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia\/Reperfusion Injury","volume":"20","author":"Silachev","year":"2015","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bbabio.2008.12.008","article-title":"An attempt to prevent senescence: A mitochondrial approach","volume":"1787","author":"Skulachev","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1134\/S0006297917070021","article-title":"Design, Synthesis, and Some Aspects of the Biological Activity of Mitochondria-Targeted Antioxidants","volume":"82","author":"Korshunova","year":"2017","journal-title":"Biochem. Mosc."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Silachev, D.N., Isaev, N.K., Pevzner, I.B., Zorova, L.D., Stelmashook, E.V., Novikova, S.V., Plotnikov, E.Y., Skulachev, V.P., and Zorov, D.B. (2012). The Mitochondria-Targeted Antioxidants and Remote Kidney Preconditioning Ameliorate Brain Damage through Kidney-to-Brain Cross-Talk. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051553"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1134\/S0006297912090052","article-title":"Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced neurological deficit in rat","volume":"77","author":"Isaev","year":"2012","journal-title":"Biochem. Mosc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1134\/S0006297910020045","article-title":"New-generation Skulachev ions exhibiting nephroprotective and neuroprotective properties","volume":"75","author":"Plotnikov","year":"2010","journal-title":"Biochem. Mosc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbadis.2010.09.008","article-title":"Mechanisms of nephroprotective effect of mitochondria-targeted antioxidants under rhabdomyolysis and ischemia\/reperfusion","volume":"1812","author":"Plotnikov","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1134\/S0006297916120154","article-title":"Dysfunction of Kidney Endothelium after Ischemia\/Reperfusion and Its Prevention by Mitochondria-Targeted Antioxidant","volume":"81","author":"Jankauskas","year":"2016","journal-title":"Biochem. Mosc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/sj.ki.5002568","article-title":"The role of mitochondria in oxidative and nitrosative stress during ischemia\/reperfusion in the rat kidney","volume":"72","author":"Plotnikov","year":"2007","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E3100","DOI":"10.1073\/pnas.1307096110","article-title":"Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection","volume":"110","author":"Plotnikov","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1134\/S000629790812002X","article-title":"Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke)","volume":"73","author":"Bakeeva","year":"2008","journal-title":"Biochem. Mosc."},{"key":"ref_28","first-page":"353","article-title":"Age-associated murine cardiac lesions are attenuated by the mitochondria-targeted antioxidant SkQ1","volume":"30","author":"Manskikh","year":"2015","journal-title":"Histol. Histopathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s12325-015-0273-6","article-title":"Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome","volume":"32","author":"Brzheskiy","year":"2015","journal-title":"Adv. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0166-4328(95)00248-0","article-title":"Long-term effects of neonatal ischemic-hypoxic brain injury on sensorimotor and locomotor tasks in rats","volume":"78","author":"Jansen","year":"1996","journal-title":"Behav. Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.nurx.2006.08.001","article-title":"Behavioral tests for preclinical intervention assessment","volume":"3","author":"Schallert","year":"2006","journal-title":"NeuroRx"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/CCM.0b013e318194abf2","article-title":"Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children","volume":"37","author":"Bayir","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Arteaga, O., \u00c1lvarez, A., Revuelta, M., Santaolalla, F., Urtasun, A., and Hilario, E. (2017). Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020265"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108251","DOI":"10.1155\/2015\/108251","article-title":"New antioxidant drugs for neonatal brain injury","volume":"2015","author":"Tataranno","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/brb3.208","article-title":"N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities","volume":"4","author":"Harrigan","year":"2014","journal-title":"Brain Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1203\/01.pdr.0000215045.91122.44","article-title":"Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats","volume":"59","author":"Jatana","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fneur.2018.00233","article-title":"Repetitive Neonatal Erythropoietin and Melatonin Combinatorial Treatment Provides Sustained Repair of Functional Deficits in a Rat Model of Cerebral Palsy","volume":"9","author":"Jantzie","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Xu, L.-X., Lv, Y., Li, Y.-H., Ding, X., Wang, Y., Han, X., Liu, M.-H., Sun, B., and Feng, X. (2017). Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: The involvement of edema related proteins. BMC Pediatr., 17.","DOI":"10.1186\/s12887-017-0824-x"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.physbeh.2016.11.029","article-title":"Effects of erythropoietin on neonatal hypoxia-ischemia brain injury in rat model","volume":"169","author":"Ren","year":"2017","journal-title":"Physiol. Behav."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.clp.2015.04.004","article-title":"Erythropoietin and Neonatal Neuroprotection","volume":"42","author":"Juul","year":"2015","journal-title":"Clin. Perinatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18886","DOI":"10.3390\/molecules201018886","article-title":"Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism","volume":"20","author":"Tan","year":"2015","journal-title":"Molecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e1135","DOI":"10.1542\/peds.2009-2268","article-title":"Human recombinant erythropoietin in asphyxia neonatorum: Pilot trial","volume":"125","author":"Elmahdy","year":"2010","journal-title":"Pediatrics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1542\/peds.2012-0498","article-title":"Erythropoietin for neuroprotection in neonatal encephalopathy: Safety and pharmacokinetics","volume":"130","author":"Wu","year":"2012","journal-title":"Pediatrics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e20160191","DOI":"10.1542\/peds.2016-0191","article-title":"High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial","volume":"137","author":"Wu","year":"2016","journal-title":"Pediatrics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/jp.2017.17","article-title":"Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: A randomized placebo-controlled trial","volume":"37","author":"Malla","year":"2017","journal-title":"J. Perinatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00232-008-9124-6","article-title":"Kinetic analysis of permeation of mitochondria-targeted antioxidants across bilayer lipid membranes","volume":"224","author":"Rokitskaya","year":"2008","journal-title":"J. Membr. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.18632\/aging.101054","article-title":"An antioxidant specifically targeting mitochondria delays progression of Alzheimer\u2019s disease-like pathology","volume":"8","author":"Stefanova","year":"2016","journal-title":"Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.12659\/MSM.894758","article-title":"Mitochondria, Chloroplasts in Animal and Plant Cells: Significance of Conformational Matching","volume":"21","author":"Stefano","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.plaphy.2013.03.014","article-title":"Functional roles of flavonoids in photoprotection: New evidence, lessons from the past","volume":"72","author":"Agati","year":"2013","journal-title":"Plant Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1399-3054.2010.01391.x","article-title":"The production and scavenging of reactive oxygen species in the plastoquinone pool of chloroplast thylakoid membranes","volume":"140","author":"Mubarakshina","year":"2010","journal-title":"Physiol. Plant."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1073\/pnas.0910216107","article-title":"Penetrating cation\/fatty acid anion pair as a mitochondria-targeted protonophore","volume":"107","author":"Severin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1006\/nbdi.2000.0371","article-title":"Early Neurodegeneration after Hypoxia-Ischemia in Neonatal Rat Is Necrosis while Delayed Neuronal Death Is Apoptosis","volume":"8","author":"Northington","year":"2001","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1073\/pnas.0808362106","article-title":"Subdivisions of primary motor cortex based on cortico-motoneuronal cells","volume":"106","author":"Rathelot","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1101\/sqb.2014.79.024786","article-title":"Internal and External Feedback Circuits for Skilled Forelimb Movement","volume":"79","author":"Azim","year":"2014","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1212\/WNL.56.12.1666","article-title":"Treatment of stroke in rat with intracarotid administration of marrow stromal cells","volume":"56","author":"Li","year":"2001","journal-title":"Neurology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1442-200X.2008.02705.x","article-title":"Neonatal rat hypoxia-ischemia: Effect of the anti-oxidant mitoquinol, and S-PBN","volume":"50","author":"Hobbs","year":"2008","journal-title":"Pediatr. Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e722","DOI":"10.1542\/peds.2008-0269","article-title":"Free radical injury and blood-brain barrier permeability in hypoxic-ischemic encephalopathy","volume":"122","author":"Kumar","year":"2008","journal-title":"Pediatrics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jbbm.2005.10.003","article-title":"Fluorescence probes used for detection of reactive oxygen species","volume":"65","author":"Gomes","year":"2005","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1523\/JNEUROSCI.4468-06.2007","article-title":"Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation","volume":"27","author":"Abramov","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1515\/jpm-2017-0070","article-title":"Experimental neonatal hypoxia ischemia causes long lasting changes of oxidative stress parameters in the hippocampus and the spleen","volume":"46","author":"Odorcyk","year":"2018","journal-title":"J. Perinat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.brainres.2008.10.017","article-title":"Long-term effects of environmental stimulation following hypoxia-ischemia on the oxidative state and BDNF levels in rat hippocampus and frontal cortex","volume":"1247","author":"Pereira","year":"2009","journal-title":"Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.192.7.1001","article-title":"Reactive oxygen species (ROS)-induced ROS release: A new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes","volume":"192","author":"Zorov","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2174\/1567202611666140520151002","article-title":"Glycogen synthase kinase-\u03b23 in ischemic neuronal death","volume":"11","author":"Hanumanthappa","year":"2014","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10517-009-0489-z","article-title":"Comparative evaluation of two methods for studies of experimental focal ischemia: Magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries","volume":"147","author":"Silachev","year":"2009","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0165-0270(91)90048-5","article-title":"The \u201cstaircase test\u201d: A measure of independent forelimb reaching and grasping abilities in rats","volume":"36","author":"Montoya","year":"1991","journal-title":"J. Neurosci. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s11055-014-9996-0","article-title":"Assessment of Long-Term Sensorimotor Deficit after Cerebral Ischemia\/Hypoxia in Neonatal Rats","volume":"44","author":"Silachev","year":"2014","journal-title":"Neurosci. Behav. Physiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/1871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:14:40Z","timestamp":1760195680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/1871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,27]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["molecules23081871"],"URL":"https:\/\/doi.org\/10.3390\/molecules23081871","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,27]]}}}