Neonatal rat hypoxia-ischemia: Effect of the anti-oxidant mitoquinol, and S-PBN

• Published in: Pediatrics international Vol. 50; no. 4; pp. 481 - 488
• Main Authors: Hobbs, Catherine E., Murphy, Michael P., Smith, Robin A.J., Oorschot, Dorothy E.
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.08.2008; Blackwell Publishing Ltd
• Subjects: Animals; Animals, Newborn; Antioxidants; Antioxidants - pharmacology; Benzenesulfonates - pharmacology; Brain damage; Cell Survival - drug effects; Corpus Striatum - drug effects; Corpus Striatum - pathology; Free radicals; Hypoxia; Hypoxia-Ischemia, Brain - pathology; medium-spiny neurons; mitoquinol (mitoQ); Neurons - drug effects; Organophosphorus Compounds - pharmacology; Pediatrics; perinatal hypoxia-ischemia; Rats; Rats, Sprague-Dawley; Rodents; S-PBN; striatum; Ubiquinone - pharmacology
• ISSN: 1328-8067; 1442-200X
• DOI: 10.1111/j.1442-200X.2008.02705.x

Background: The production of oxygen free radicals after perinatal hypoxia–ischemia is thought to play a critical role in the pathogenesis of the brain injury. Administration of anti‐oxidants may thus be neuroprotective. The aim of the present study was to investigate the effect of a mitochondria‐targeted anti‐oxidant mitoquinol (mitoQ) administered in the form of the prodrug mitoquinone, and an extracellular anti‐oxidant N‐tert‐butyl‐(2‐sulfophenyl)‐nitrone (S‐PBN; Aldrich, St Louis, MO, USA), on neuronal survival in the rat striatum after acute perinatal hypoxia–ischemia. Methods: Mitoquinone at 17 μmol/L (n = 6) or 51 μmol/L (n = 6), or its diluent (n = 12), was continuously infused over 3 days into the right striatum of Sprague–Dawley rats. Infusion was via an Alzet micro‐osmotic pump (Alza, Los Angeles, CA, USA), stereotaxically implanted on postnatal day (PN) 7 under anesthesia. In another experiment, S‐PBN (100 mg/kg) (n = 8) or its diluent (n = 8) was administered in six s.c. injections every 12 h from the evening of PN7. Hypoxia–ischemia was induced on PN8 by right common carotid artery ligation under anesthesia, followed 2.5 h later by exposure to 8% oxygen for 1.5 h. On PN14 the pups were euthanased and 40 μm serial sections were cut through the entire striatum. The total number of medium‐spiny neurons within the right striatum was stereologically determined using the optical disector/Cavalieri method. Results: No significant difference was seen in the total number of striatal medium‐spiny neurons between the 17 μmol/L or 51 μmol/L mitoQ‐treated pups and their respective diluent‐treated controls. No significant difference was seen in the total number of striatal medium‐spiny neurons between the S‐PBN‐treated and diluent‐treated pups. Conclusion: Solely targeting mitochondrial oxidants with mitoQ, or extracellular oxidants with S‐PBN, is not protective for striatal medium‐spiny neurons after perinatal hypoxia–ischemia.