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

Neurosci Lett. 2013 May 10;542:65-70. doi: 10.1016/j.neulet.2013.02.035. Epub 2013 Feb 28.

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 500mg/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 500mg/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 500mg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain / drug effects*
  • Brain / pathology
  • Brain Infarction / drug therapy
  • Brain Infarction / pathology
  • Caspase 3 / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / pathology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / pathology
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Uridine / therapeutic use*

Substances

  • Neuroprotective Agents
  • Caspase 3
  • Uridine