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Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain
Journal article   Open access   Peer reviewed

Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain

Panagiotis Kratimenos, Evan Z. Goldstein, Ioannis Koutroulis, Susan Knoblach, Beata Jablonska, Payal Banerjee, Shadi N. Malaeb, Surajit Bhattacharya, M. Isabel Almira-Suarez, Vittorio Gallo, …
iScience, v 23(12), 101766
18 Dec 2020
DOI: https://doi.org/10.1016/j.isci.2020.101766
PMID: 33294779
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.isci.2020.101766View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Developmental Neuroscience Porcine Molecular Biology Transcriptomics
Acute hypoxia (HX) causes extensive cellular damage in the developing human cerebral cortex. We found increased expression of activated-EGFR in affected cortical areas of neonates with HX and investigated its functional role in the piglet, which displays a highly evolved, gyrencephalic brain, with a human-like maturation pattern. In the piglet, HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation, and reversed HX-induced astrogliosis. We performed for the first time high-throughput transcriptomic analysis of the piglet cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in piglet and human brain injury. Our results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain. [Display omitted] •EGFR mediates the effects of neonatal hypoxia in piglet and human cerebral cortex•EGFR inhibition reverses pathological changes induced by hypoxia in piglet cortex•EGFR blockage prevents hypoxia-induced transcriptomic changes in piglet cortex•EGFR-associated pathways are therapeutic targets in neonatal hypoxic injury Porcine Molecular Biology; Developmental Neuroscience; Transcriptomics

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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