Erythropoietin Improves Atrophy, Bleeding and Cognition in the Newborn Intraventricular Hemorrhage.

Carmen Hierro-Bujalance,Angel Del Marco,Monica Garcia-Alloza,Simon Lubian-Lopez,Marcos Bernal-Martin,Isabel Benavente-Fernandez,Carmen Infante-Garcia,Carmen Maria Mengual-Gonzalez,Daniel Sanchez-Sotano,Ana Casado-Revuelta,Carmen Lucena-Porras

doi:10.3389/fcell.2020.571258

Abstract

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most devastating complications of prematurity. The short- and long-term neurodevelopmental consequences after severe GM-IVH are a major concern for neonatologists. These kids are at high risk of psychomotor alterations and cerebral palsy; however, therapeutic approaches are limited. Erythropoietin (EPO) has been previously used to treat several central nervous system complications due to its role in angiogenesis, neurogenesis and as growth factor. In addition, EPO is regularly used to reduce the number of transfusions in the preterm infant. Moreover, EPO crosses the blood-brain barrier and EPO receptors are expressed in the human brain throughout development. To analyze the role of EPO in the GM-IVH, we have administered intraventricular collagenase (Col) to P7 mice, as a model of GM-IVH of the preterm infant. After EPO treatment, we have characterized our animals in the short (14 days) and the long (70 days) term. In our hands, EPO treatment significantly limited brain atrophy and ventricle enlargement. EPO also restored neuronal density and ameliorated dendritic spine loss. Likewise, inflammation and small vessel bleeding were also reduced, resulting in the preservation of learning and memory abilities. Moreover, plasma gelsolin levels, as a feasible peripheral marker of GM-IVH-induced damage, recovered after EPO treatment. Altogether, our data support the positive effect of EPO treatment in our preclinical model of GM-IVH, both in the short and the long term.

Highlights

Every year there are over 15 million preterm births and ∼7% of these kids suffer long term neurodevelopmental impairment (Maxwell et al, 2017)
The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most common complications observed in the preterm infant (PTI) (Tan et al, 2018)
While the incidence of GM-IVH has declined since the 1990s, due to improvements in neonatal care, the increased survival of extremely PTI has contributed to Erythropoietin for Intraventricular Hemorrhage maintain the absolute number of GM-IVH very high (Mukerji et al, 2015)

Summary

Introduction

Every year there are over 15 million preterm births and ∼7% of these kids suffer long term neurodevelopmental impairment (Maxwell et al, 2017). The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most common complications observed in the preterm infant (PTI) (Tan et al, 2018). The shortand long-term neurodevelopmental complications in the PTI with severe or even mild GM-IVH are a major concern, since these kids are at high risk of neurosensory impairment, developmental delay, cerebral palsy, deafness, psychomotor alterations or cerebral palsy (Ballabh, 2010; Mukerji et al, 2015; Benavente-Fernandez et al, 2018)

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