摘要：SummaryAcute 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.Graphical AbstractDisplay OmittedHighlights•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 injuryPorcine Molecular Biology; Developmental Neuroscience; Transcriptomics
