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Repeated Neonatal Isoflurane Exposure is Associated with Higher Susceptibility to Chronic Variable Stress-induced
Luofang Peng1, Maoen Zhu2, Yong Yang2
1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha City, Hunan Province, PR China; Department of Anaesthesiology and Operating Theatre Services, Xiangya Hospital of Central South University, Changsha City, Hunan Province, PR China.
Insights
Early exposure to the anesthetic isoflurane in mice increases anxiety and neuroinflammation when combined with chronic variable stress (CVS). This early anesthetic exposure primes the brain, making it more susceptible to stress-induced behavioral and inflammatory changes later in life.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Early-life exposure to anesthetics can negatively impact brain development.
- Research has primarily focused on neurocognitive deficits, with less attention paid to long-term neuropsychiatric outcomes.
Purpose of the Study:
- To investigate the effects of repeated neonatal isoflurane exposure on chronic variable stress (CVS)-induced psychiatric and behavioral outcomes.
- To examine CVS-related neuronal activity and neuroinflammatory responses in relevant brain circuits following early isoflurane exposure.
Main Methods:
- C57BL/6J mice received three isoflurane exposures or a control exposure on postnatal days 7-9.
- From postnatal day 45, mice underwent a 3-week CVS paradigm or served as controls.
- Behavioral tests assessed neuropsychiatric performance; neuronal activity was measured by ΔFosB immunopositivity; neuroinflammation was assessed by analyzing pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α).
Main Results:
- Neonatal isoflurane exposure significantly enhanced anxiety levels post-CVS.
- Enhanced neuronal activity (ΔFosB) and exacerbated neuroinflammation were observed in the basolateral amygdaloid nuclei (BLA) and hippocampal dentate gyrus (DG) in mice with prior isoflurane exposure.
- Control mice showed no such changes.
Conclusions:
- Early, repeated isoflurane exposure in mice is associated with increased susceptibility to CVS-evoked anxiety.
- This heightened susceptibility is accompanied by increased neuronal activity in the BLA and DG and heightened inflammatory responses to CVS.
Abstract:
Numerous studies have reported that prolonged or multiple exposures to anaesthetics in early life lead to detrimental effects on brain function, most having focused on neurocognitive function, and relatively few on long term neuropsychiatric performance. The present study investigated the impact of repeated neonatal isoflurane exposure on chronic variable stress (CVS)-induced psychiatric and behavioural outcomes together with CVS-related neuronal activity and neuro-inflammatory reactivity in relevant brain circuits. In the present study, C57BL/6J mice received either three exposures to isoflurane at postnatal days 7, 8, and 9 or a control exposure. From postnatal day 45, mice were exposed to a mild, 3-week, CVS paradigm or none and the CVS-related neuropsychiatric performance was evaluated using a series of behavioural tests. The neuronal activity in relevant brain regions was measured by ΔFosB immunopositivity and CVS-related neuroinflammation was assessed by analysing levels of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α. In mice experiencing serial neonatal isoflurane exposure, we detected a significant enhancement in anxiety levels following CVS procedures, together with enhanced neuronal activity, and exacerbated neuroinflammation in the basolateral amygdaloid nuclei (BLA) and hippocampal dentate gyrus (DG) regions. No such change was found in control mice. These results indicate an association between early multiple isoflurane exposures in infant mice and susceptibility to a CVS-evoked anxious phenotype accompanied by enhanced neuronal activity in BLA and DG regions and high inflammatory reactivity in response to CVS.
