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

TitleNeonatal rat hypoxia-ischemia: Effect of the anti-oxidant mitoquinol, and S-PBN.
Publication TypeJournal Article
Year of Publication2008
AuthorsHobbs, CE, Murphy, MP, Smith, RAJ, Oorschot, DE
JournalPediatr Int
Volume50
Issue4
Pagination481-8
Date Published2008 Aug
ISSN1442-200X
KeywordsAnimals, Animals, Newborn, Antioxidants, Benzenesulfonates, Cell Survival, Corpus Striatum, Hypoxia-Ischemia, Brain, Neurons, Organophosphorus Compounds, Rats, Rats, Sprague-Dawley, Ubiquinone
Abstract

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 micromol/L (n = 6) or 51 micromol/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 microm 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 micromol/L or 51 micromol/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.

DOI10.1111/j.1442-200X.2008.02705.x
Alternate JournalPediatr Int
Citation Key10.1111/j.1442-200X.2008.02705.x
PubMed ID18937752
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom