Long-Term Effects of Neonatal Single or Multiple Isoflurane Exposures on Spatial Memory in Rats
Open Access
- 1 January 2013
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Neurology
- Vol. 4, 47403
- https://doi.org/10.3389/fneur.2013.00087
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.This publication has 41 references indexed in Scilit:
- Attention-Deficit/Hyperactivity Disorder After Early Exposure to Procedures Requiring General AnesthesiaMayo Clinic Proceedings, 2012
- Ketamine-induced Neuroapoptosis in the Fetal and Neonatal Rhesus Macaque BrainAnesthesiology, 2012
- Are anaesthetics toxic to the brain?British Journal of Anaesthesia, 2011
- Rats Exposed to Isoflurane In Utero during Early Gestation Are Behaviorally Abnormal as AdultsAnesthesiology, 2011
- Early childhood general anaesthesia exposure and neurocognitive developmentBritish Journal of Anaesthesia, 2010
- Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal MiceAnesthesiology, 2010
- Isoflurane Anesthesia Induced Persistent, Progressive Memory Impairment, Caused a Loss of Neural Stem Cells, and Reduced Neurogenesis in Young, but Not Adult, RodentsJournal of Cerebral Blood Flow & Metabolism, 2010
- Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth CohortAnesthesiology, 2009
- Response to neonatal anesthesia: Effect of sex on anatomical and behavioral outcomeNeuroscience, 2008
- Extrapolating brain development from experimental species to humansNeuroToxicology, 2007