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Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets
Journal article   Open access   Peer reviewed

Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets

Karen Fritz, Georgios Sanidas, Rodolfo Cardenas, Javid Ghaemmaghami, Chad Byrd, Gabriele Simonti, Adriana Valenzuela, Ignacio Valencia, Maria Delivoria-Papadopoulos, Vittorio Gallo, …
eNeuro, v 11(3)
Mar 2024
DOI: https://doi.org/10.1523/ENEURO.0268-23.2023
PMID: 38233145
url
https://doi.org/10.1523/ENEURO.0268-23.2023View
Published, Version of Record (VoR) Open

Abstract

Animals Animals, Newborn Cognition Hypercapnia - complications Respiration, Artificial - methods Swine Cerebral Cortex
In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.

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