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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
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Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing
Kevin D Broad1, Go Kawano1, Igor Fierens1
1Institute for Women's Health, University College London, London, United Kingdom.
Plos One
|March 30, 2017
Summary
Minor surgery in neonatal piglets, combined with anesthesia, significantly increased brain cell death and altered gene expression compared to anesthesia alone. This suggests surgery itself may impact brain development and cognitive function.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- General anesthesia in infancy may negatively impact neural and cognitive development.
- Previous human studies are inconclusive due to the confounding factor of surgery.
- Surgery itself might contribute to adverse neurodevelopmental outcomes.
Purpose of the Study:
- To investigate if minor surgery, in addition to anesthesia, increases brain cell death in neonates.
- To determine if surgery disrupts neurodevelopmental and cognitive gene transcription in the neonatal brain.
- To explore mechanisms by which surgery influences brain development independently or with anesthesia.
Main Methods:
- Neonatal male piglets were randomly assigned to receive 6 hours of isoflurane anesthesia or anesthesia plus 15 minutes of inguinal hernia repair surgery.
- Brain cell death was assessed in multiple brain regions.
- RNA sequencing (RNAseq) was performed on brain tissue to analyze gene expression changes.
Main Results:
- Surgery significantly increased brain cell death in eight brain areas compared to anesthesia alone.
- Surgery induced significant changes in 181 gene transcripts in the cingulate cortex.
- Pathway analysis indicated surgery influences thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS, and GABAA signaling pathways.
Conclusions:
- Minor surgical procedures in the neonatal period, even when combined with anesthesia, can increase brain cell death.
- Surgery alters the expression of genes involved in critical neural pathways, suggesting a direct impact on neurodevelopment.
- These findings highlight potential mechanisms by which surgery, independent of anesthesia, may affect neonatal brain development and cognitive outcomes.
