A novel, clinically relevant use of a piglet model to study the effects of anesthetics on the developing brain

• DOI: 10.1186/s40169-015-0079-9
• Publication Date: 2016-01-12T14:37:13Z
• Authors: Emmett E. Whitaker; Bruno Bissonnette; Andrew D. Miller; Tanner L. Koppert; Joseph D. Tobias; Christopher R. Pi...; Fievos L. Christofi
• Keywords: Entorhinal cortex

Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms action may be undertaken. The goal study was to develop novel, clinically relevant, translational way use piglet investigate anesthesia effects on brain.29 newborn piglets were assigned either: (1) control (no intervention, n = 10); (2) lipopolysaccharide (LPS; positive inflammatory control, 9); or (3) isoflurane (n 10). Positive animals given 100 mcg/kg LPS from Escherichia coli intraperitoneally (IP) same day as those receiving isoflurane. Isoflurane administered for 3 h while care taken ensure human perioperative conditions. To establish clinical scenario, each intubated monitored with pulse oximetry, invasive non-invasive blood pressure, electrocardiogram, temperature, end-tidal CO2, anesthetic concentration, iSTAT analysis. All sacrificed after 48 using transcardiac perfusion ice-cold, heparinized phosphate buffered saline (PBS) followed by 4 % paraformaldehyde (PFA). Brains collected histopathological analysis focused entorhinal cortex looking degenerative changes due its critical role learning memory. Reliable achieved colored ink surface brains, which then cross-referenced microscopic anatomy. Hematoxylin & eosin-stained high-power fields used quantify cells. ImageJ™ (National Institutes Health, Bethesda, MD, USA) count absolute number progenitor glial cells (PGC) PGCs per cluster. Immunohistochemistry also utilized cellular structures.Histopathological sections 28 brains analyzed. One group died shortly administration, presumably inadvertent intravascular injection. There acute basal ganglia ischemic infarct one isoflurane-treated animal. A large small, round nucleated seen throughout layer II all animals. These identified immunohistochemistry light microscopy. Although there no difference between groups, demonstrated significant increase forming 'clusters' cortex. An apparent change pattern doublecortin labeling suggests neuronal precursors undifferentiated neurons.This represents first novel relevant neonatal brain. induces neuroinflammation, is potential mechanism perhaps causing cell distribution. We postulate that isoflurane-induced distribution could have important implications differentiation, maturation neural circuit behavior rapidly