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Updated: Mar 11, 2026
Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Isoflurane Exposure Induces Cell Death, Microglial Activation and Modifies the Expression of Genes Supporting
Kevin D Broad1, Jane Hassell1, Bobbi Fleiss2,3,4
1Institute for Women's Health, University College London, London, United Kingdom.
Insights
General anesthesia, like isoflurane, can harm infant brain development by increasing cell death and inflammation. This study in piglets shows isoflurane disrupts genes crucial for neural plasticity and memory.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- General anesthesia exposure in early infancy may negatively impact neural and cognitive development.
- Mechanisms are complex, not fully understood, and may be sexually dimorphic.
- Potential mechanisms include apoptosis, inflammation, and disrupted gene expression.
Purpose of the Study:
- To investigate the effects of 6-hour isoflurane exposure on cell death, microglial activation, and gene expression in the male neonatal piglet brain.
- To explore potential mechanisms of anesthesia-induced neurodevelopmental and cognitive deficits.
Main Methods:
- Neonatal piglets were randomized to naive controls or 6-hour isoflurane exposure.
- Cell death (TUNEL, caspase-3) and microglial activation were assessed in 7 brain regions.
- Gene expression changes were analyzed using microarray and qPCR in the cingulate cortex; electroencephalography (EEG) was recorded.
Main Results:
- Isoflurane significantly increased cell death (neurons and oligodendrocytes) in multiple brain regions, including the cortex, hippocampus, and thalamus.
- Microglial activation was observed in several brain regions, indicating an inflammatory response.
- Isoflurane disrupted the expression of 79 gene transcripts, including those vital for transcription control, neural plasticity, and memory formation.
Conclusions:
- Isoflurane exposure increases apoptosis and inflammation in the neonatal piglet brain.
- Isoflurane disrupts gene expression related to neural circuit development, adaptive responses, and memory.
- These findings suggest novel mechanisms by which isoflurane may adversely affect neural and cognitive development.
Abstract:
Exposure of the brain to general anesthesia during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex, incompletely understood and may be sexually dimorphic, but include developmentally inappropriate apoptosis, inflammation and a disruption to cognitively salient gene expression. We investigated the effects of a 6h isoflurane exposure on cell death, microglial activation and gene expression in the male neonatal piglet brain. Piglets (n = 6) were randomised to: (i) naive controls or (ii) 6h isoflurane. Cell death (TUNEL and caspase-3) and microglial activation were recorded in 7 brain regions. Changes in gene expression (microarray and qPCR) were assessed in the cingulate cortex. Electroencephalography (EEG) was recorded throughout. Isoflurane anesthesia induced significant increases in cell death in the cingulate and insular cortices, caudate nucleus, thalamus, putamen, internal capsule, periventricular white matter and hippocampus. Dying cells included both neurons and oligodendrocytes. Significantly, microglial activation was observed in the insula, pyriform, hippocampus, internal capsule, caudate and thalamus. Isoflurane induced significant disruption to the expression of 79 gene transcripts, of these 26 are important for the control of transcription and 23 are important for the mediation of neural plasticity, memory formation and recall. Our observations confirm that isoflurane increases apoptosis and inflammatory responses in the neonatal piglet brain but also suggests novel additional mechanisms by which isoflurane may induce adverse neural and cognitive development by disrupting the expression of genes mediating activity dependent development of neural circuits, the predictive adaptive responses of the brain, memory formation and recall.
