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.
Highlights
Exposure to anesthetic agents early in development can cause neurotoxicity and neonatal exposure in rodents is associated with persistent deficits in cognition in later adulthood, in learning and memory [1, 2]
The principal finding of this study is that repeated exposure to isoflurane during development is associated with greater longterm impairment, in the ability of adult rats to acquire and perform a spatial memory task, than single exposure
Single exposure to isoflurane revealed an unexpected apparent facilitatory effect in males, with single-exposed males completing the maze faster than male controls, and making more choices before the first error occurred. These findings support the view that repeated exposures to general anesthesia during development is associated with greater long-term cognitive impairment than single exposure
Summary
Exposure to anesthetic agents early in development can cause neurotoxicity and neonatal exposure in rodents is associated with persistent deficits in cognition in later adulthood, in learning and memory [1, 2]. These deficits have been demonstrated following exposure to a variety of anesthetic agents [3,4,5] and are not restricted to agents of a particular drug class. There are, likely to be other mechanisms by which anesthesia causes neural dysfunction and cognitive impairment, including disturbances in synaptic morphology in surviving neurons (for review 17)
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