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

• Published in: Neuroscience letters 2013-05, Vol.542, p.65-70
• Main Authors: Cansev, Mehmet, Minbay, Zehra, Goren, Bulent, Yaylagul, Esra Orenlili, Cetinkaya, Merih, Koksal, Nilgun, Alkan, Tulin
• Format: Article
• Language: English
• Subjects: 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; Hypoxic–ischemic encephalopathy; Neonatal; Neuroprotection; Neuroprotective Agents - therapeutic use; Rat; Rats; Rats, Sprague-Dawley; Uridine; Uridine - therapeutic use
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2013.02.035

► Uridine is the principal pyrimidine in humans and a membrane phospholipid precursor. ► Uridine treatment reduces brain infarction and apoptosis in rat neonatal HIE model. ► This is the first study to report cerebroprotection by uridine in rat neonatal HIE. 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.