Differential short-term regional effects of early high dose erythropoietin on white matter in preterm lambs after mechanical ventilation

The Journal of Physiology
Samantha K BartonMary Tolcos

Abstract

Inadvertently injurious ventilation of preterm neonates in the delivery room can cause cerebral white matter (WM) inflammation and injury. We investigated the impact of an early high dose of recombinant human erythropoietin (EPO) on ventilation-induced WM changes in preterm lambs. Injurious ventilation, targeting a V(T) of 15 ml kg(-1) with no positive end-expiratory pressure, was initiated for 15 min in preterm lambs (0.85 gestation). Conventional ventilation was continued for a further 105 min. Lambs received either 5000 IU kg(-1) of EPO (EPREX®; Vent+EPO; n = 6) or vehicle (Vent; n = 8) via an umbilical vein at 4 ± 2 min. Markers of WM injury and inflammation were assessed using quantitative real-time PCR (qPCR) and immunohistochemistry and compared to a group of unventilated controls (UVC; n = 4). In Vent+EPO lambs compared to Vent lambs: (i) interleukin (IL)-1β and IL-6 mRNA levels in the periventricular WM and IL-8 mRNA levels in the subcortical WM were higher (P < 0.05 for all); (ii) the density of microglia within the aggregations was not different in the periventricular WM and was lower in the subcortical WM (P = 0.001); (iii) the density of astrocytes was lower in the subcortical WM (P = 0.002); (iv) occludin and clau...Continue Reading

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Citations

Mar 2, 2016·The Journal of Physiology·D A GiussaniA L Fowden
Nov 2, 2018·Journal of Applied Physiology·Beth J AllisonGraeme R Polglase
Nov 12, 2016·Molecular BioSystems·Vladimir N Uversky, Elrashdy M Redwan
Dec 1, 2015·Frontiers in Pediatrics·Samantha K BartonGraeme R Polglase
May 26, 2021·The Journal of Physiology·Simerdeep K DhillonLaura Bennet

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