Uridine treatment protects against neonatal brain damage and long-term cognitive deficits caused by hyperoxia


GÖREN B., ÇAKIR A., Sevinc C., Kocoglu S. S. , ÖCALAN B., OY C., ...More

BRAIN RESEARCH, vol.1676, pp.57-68, 2017 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 1676
  • Publication Date: 2017
  • Doi Number: 10.1016/j.brainres.2017.09.010
  • Journal Name: BRAIN RESEARCH
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.57-68
  • Keywords: Hyperoxia, Brain injury, Uridine, Neonatal rat, Behavior, Learning and memory, INDUCED CELL-DEATH, WATER-MAZE, RAT MODEL, INJURY, OXYGEN, ERYTHROPOIETIN, OLIGODENDROCYTES, PATHOGENESIS, CYTIDINE, VOLUMES

Abstract

Exposure to excessive oxygen in survivors of preterm birth is one of the factors that underlie the adverse neurological outcome in later life. Various pathological changes including enhanced apoptotic activity, oxidative stress and inflammation as well as decreased neuronal survival has been demonstrated in animal models of neonatal hyperoxia. The aim of the present study was to investigate the effect of administering uridine, an anti-apoptotic agent, on cellular, molecular and behavioral consequences of hyperoxia-induced brain damage in a neonatal rat model. For five days from birth, rat pups were either subjected continuously to room air (21% oxygen) or hyperoxia (80% oxygen) and received daily intraperitoneal (i.p.) injections of saline (0.9% NaCl) or uridine (500 mg/kg). Two-thirds of all pups were sacrificed on postnatal day 5 (P5) in order to investigate apoptotic cell death, myelination and number of surviving neurons. One-thirds of pups were raised through P40 in order to evaluate early reflexes, sensorimotor coordination and cognitive functions followed by investigation of neuron count and myelination. We show that uridine treatment reduces apoptotic cell death and hypomyelination while increasing the number of surviving neurons in hyperoxic pups on P5. In addition, uridine enhances learning and memory performances in periadolescent rats on P40. These data suggest that uridine administered during the course of hyperoxic insult enhances cognitive functions at periadolescent period probably by reducing apoptotic cell death and preventing hypomyelination during the neonatal period in a rat model of hyperoxia-induced brain injury. (C) 2017 Elsevier B.V. All rights reserved.