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

[Display omitted] •Hyperoxia causes neuro-glial damage in developing rat brain.•Uridine reduces apoptosis in a neonatal rat model of hyperoxia-induced brain injury.•Uridine prevents hyperoxia-induced hypomyelination.•Cognitive deficits are ameliorated by uridine treatment at periadolescent period. E...

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Bibliographic Details
Published in:Brain research 2017-12, Vol.1676, p.57-68
Main Authors: Goren, Bulent, Cakir, Aysen, Sevinc, Cansu, Serter Kocoglu, Sema, Ocalan, Busra, Oy, Ceren, Minbay, Zehra, Kahveci, Nevzat, Alkan, Tulin, Cansev, Mehmet
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Apoptosis - drug effects
Behavior
Brain - drug effects
Brain - growth & development
Brain - pathology
Brain - physiopathology
Brain Injuries - drug therapy
Brain Injuries - pathology
Brain Injuries - physiopathology
Brain Injuries - psychology
Brain injury
Cell Count
Cell Survival - drug effects
Cognitive Dysfunction - pathology
Cognitive Dysfunction - physiopathology
Cognitive Dysfunction - prevention & control
Disease Models, Animal
Female
Hyperoxia
Hyperoxia - drug therapy
Hyperoxia - pathology
Hyperoxia - physiopathology
Hyperoxia - psychology
Learning and memory
Learning Disorders - pathology
Learning Disorders - physiopathology
Learning Disorders - prevention & control
Male
Myelin Sheath - drug effects
Myelin Sheath - pathology
Neonatal rat
Neurons - drug effects
Neurons - pathology
Neuroprotective Agents - pharmacology
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Rats, Sprague-Dawley
Uridine
Uridine - pharmacology
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Summary:[Display omitted] •Hyperoxia causes neuro-glial damage in developing rat brain.•Uridine reduces apoptosis in a neonatal rat model of hyperoxia-induced brain injury.•Uridine prevents hyperoxia-induced hypomyelination.•Cognitive deficits are ameliorated by uridine treatment at periadolescent period. 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 (500mg/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.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2017.09.010