Hypoxia induced periventricular white matter damage in the developing brain

Abstract

Normal development and maturation of the brain are affected by hypoxia. The white matter peripheral to the lateral ventricles, called periventricular white matter (PWM), is selectively vulnerable to hypoxic damage in premature infants. PWM damage (PWMD) contributes significantly to neonatal mortality and long‐term neurodevelopmental deficits such as cerebral palsy, impaired vision, hearing impairments and mental retardation. This study investigated the hypoxic damage to the PWM in the neonatal brain and the potential of melatonin in ameliorating the damage. PWM of 1‐day old rats was examined at 3 hours to 7days after hypoxic exposure. Vascular endothelial growth factor (VEGF), nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) content in the PWM was examined following the hypoxic exposure. VEGF, NO and MDA concentration was increased whereas that of GSH was reduced in the PWM after the hypoxic exposure. Along with the above, degenerating axons, apoptotic and necrotic cells and vacuolation of capillary endothelial cells was observed. The neighbouring ependymal and choroid plexus in the lateral ventricles also appeared to undergo structural alteration. Increased vascular permeability in the PWM of hypoxic rats was evidenced by the leakage of rhodamine isothiocyanate (RhIC) which was taken up by the amoeboid microglial cells. Hypoxic rats treated with melatonin showed decreased VEGF, NO and MDA concentration, increased GSH content and reduced RhIC leakage in the PWM. The ultrastructure of axons, endothelial, ependymal and choroid plexus cells appeared relatively normal in the hypoxic animals treated with melatonin. The results of this study suggest that melatonin has the potential to protect the developing white matter against hypoxic damage and its protective effect was possibly due to its antioxidant properties.