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

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.

Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury.

Background: Neonatal hypoxic brain injury is a major cause of intellectual and developmental disability. Hypoxia causes neuronal dysfunction and death in the developing cerebral cortex due to excitotoxic Ca-influx. In the translational piglet model of hypoxic encephalopathy, we have previously shown that hypoxia overactivates Ca/Calmodulin (CaM) signaling via Sarcoma (Src) kinase in cortical neurons, resulting in overexpression of proapoptotic genes.

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

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 Ca/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia.

Biomechanical Responses of Neonatal Brachial Plexus to Mechanical Stretch.

This study investigated the biomechanical responses of neonatal piglet brachial plexus (BP) segments-root/trunk, chord, and nerve at two different rates, 0.01 mm/second (quasistatic) and 10 mm/second (dynamic)-and compared their response to another peripheral nerve (tibial). Comparisons of mechanical responses at two different rates reported a significantly higher maximum load, maximum stress, and Young's modulus (E) values when subjected to dynamic rate.

Effect of Src Kinase inhibition on Cytochrome c, Smac/DIABLO and Apoptosis Inducing Factor (AIF) Following Cerebral Hypoxia-Ischemia in Newborn Piglets.

We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI).