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Published on: December 4, 2013
Long-term effects of neonatal single or multiple isoflurane exposures on spatial memory in rats
Kathy L Murphy1, Mark G Baxter
1Department of Experimental Psychology, University of Oxford , Oxford , UK ; Glickenhaus Laboratory of Neuropsychology, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
Insights
Repeated exposure to general anesthetics in neonatal rats caused long-term spatial memory deficits. A single exposure unexpectedly improved memory, suggesting cumulative anesthetic exposure is more detrimental to cognitive development.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Neonatal exposure to general anesthetics is neurotoxic in animal models, potentially causing long-term cognitive deficits.
- Human data suggest early-life anesthetic exposure may harm cognitive development, with multiple exposures being particularly damaging.
Purpose of the Study:
- To investigate if repeated neonatal anesthesia exposure in rats leads to long-term cognitive impairments.
- To compare the magnitude of cognitive impairment from single versus multiple anesthetic exposures.
Main Methods:
- Neonatal Long-Evans rats were exposed to isoflurane (1.8% for 2 hours) on postnatal day 7 (single exposure) or on days 7, 10, and 13 (repeated exposure).
- Spatial working memory was assessed in adulthood (postnatal day 91) using a standardized task.
Main Results:
- Rats with repeated isoflurane exposure exhibited significant impairments in spatial working memory compared to controls.
- Male rats receiving a single isoflurane exposure showed an unexpected facilitation in spatial memory performance.
- The cognitive deficits in the repeated exposure group were more pronounced than in the single exposure group.
Conclusions:
- Multiple neonatal exposures to general anesthesia are associated with greater long-term cognitive impairment than a single exposure.
- Findings align with human studies indicating long-term cognitive deficits after multiple, but not single, early-life anesthetic exposures.
Abstract:
General anesthetics are neurotoxic to neonatal rodents and non-human primates. Neonatal exposure to general anesthetics has been associated with long-term cognitive deficits in animal models. Some data from humans are consistent with long-term deleterious effects of anesthetic exposure early in life on cognitive development, with multiple exposures to general anesthetics being particularly damaging. We sought to determine whether repeated exposure of neonatal rats to anesthesia was associated with long-term cognitive impairments and whether the magnitude of impairments was greater than that resulting from a single exposure. Male or female Long-Evans rat pups were exposed to 1.8% isoflurane for 2 h on postnatal day (P) 7, or for 2 h each on P7, P10, and P13. Testing in a spatial working memory task began on P91. Rats that were repeatedly exposed to isoflurane were impaired relative to controls in the spatial working memory task. Male rats that received a single exposure to isoflurane showed an unexpected facilitation in spatial memory performance. These results support the hypothesis that multiple neonatal exposures to general anesthesia are associated with greater long-term cognitive impairment than a single exposure. The findings are congruent with human epidemiological studies reporting long-term cognitive impairments following multiple but not single general anesthetics early in life.
