Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury
AbstractNeonatal hypoxia–ischemia 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–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia 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–ischemia. 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–ischemia, 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. View Full-Text
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Silachev, D.N.; Plotnikov, E.Y.; Pevzner, I.B.; Zorova, L.D.; Balakireva, A.V.; Gulyaev, M.V.; Pirogov, Y.A.; Skulachev, V.P.; Zorov, D.B. Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury. Molecules 2018, 23, 1871.
Silachev DN, Plotnikov EY, Pevzner IB, Zorova LD, Balakireva AV, Gulyaev MV, Pirogov YA, Skulachev VP, Zorov DB. Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury. Molecules. 2018; 23(8):1871.Chicago/Turabian Style
Silachev, Denis N.; Plotnikov, Egor Y.; Pevzner, Irina B.; Zorova, Ljubava D.; Balakireva, Anastasia V.; Gulyaev, Mikhail V.; Pirogov, Yury A.; Skulachev, Vladimir P.; Zorov, Dmitry B. 2018. "Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury." Molecules 23, no. 8: 1871.
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