Neuroprotective effects of uridine in a rat model of neonatal hypoxic-ischemic encephalopathy


Cansev M. , Minbay Z. , Gören B. , Yaylagul E. O. , Cetinkaya M., Koksal N. , ...More

NEUROSCIENCE LETTERS, vol.542, pp.65-70, 2013 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 542
  • Publication Date: 2013
  • Doi Number: 10.1016/j.neulet.2013.02.035
  • Title of Journal : NEUROSCIENCE LETTERS
  • Page Numbers: pp.65-70
  • Keywords: Uridine, Neonatal, Hypoxic-ischemic encephalopathy, Neuroprotection, Apoptosis, Rat, DEPRIVATION-INDUCED DEATH, CDP-CHOLINE LEVELS, DOCOSAHEXAENOIC ACID, BRAIN-DAMAGE, CYTIDINE, NUCLEOTIDES, HYPOTHERMIA, PREVENTS, PLASMA, GROWTH

Abstract

Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of neurological disability requiring newer therapeutic strategies. Uridine is the principal circulating pyrimidine in humans and a substrate for nucleotides and membrane phospholipids. The objective of this study was to investigate the effects of uridine in a neonatal rat model of HIE. Rat pups subjected to hypoxic ischemic insult on postnatal day 7 were injected intraperitoneally with either saline or uridine (100, 300 or 500 mg/kg) for three consecutive days and brains were collected for evaluation of brain infarct volume and apoptosis. Compared with Control group, uridine at 300 and 500 mg/kg doses significantly reduced percent infarct volume, TUNEL(+) cell ratio and active Caspase-3 immunoreactivity in the cortex, as well as in CA1 and CA3 regions of the hippocampus. Uridine (300 and 500 mg/kg) also decreased active Caspase-3 expression in the ipsilateral hemisphere. These data indicate that uridine dose-dependently reduces brain injury in a rat model of neonatal HIE by decreasing apoptosis. (C) 2013 Elsevier Ireland Ltd. All rights reserved.