title: Acute and Long-Term Effects of Brief Sevoflurane Anesthesia During the Early Postnatal Period in Rats.
abstract: The possibility that exposure to general anesthetics during early life results in long-term impairment of neural function attracted considerable interest over the past decade. Extensive laboratory data suggest that administration of these drugs during critical stages of central nervous system development can lead to cell death, impaired neurogenesis, and synaptic growth as well as cognitive deficits. These observations are corroborated by several recent human epidemiological studies arguing that such cognitive impairment might also occur in humans. Despite the potential public health importance of this issue, several important questions remain open. Amongst them, how the duration of anesthesia exposure impact on outcome is as yet not fully elucidated. To gain insight into this question, here we focused on the short- and long-term impact of a 30-min-long exposure to clinically relevant concentrations of sevoflurane in rat pups at 2 functionally distinct stages of the brain growth spurt. We show that this treatment paradigm induced developmental stage-dependent and brain region-specific acute but not lasting changes in dendritic spine densities. Electrophysiological recordings in hippocampal brain slices from adult animals exposed to anesthesia in the early postnatal period revealed larger paired-pulse facilitation but no changes in the long-term potentiation paradigm when compared with nonanesthetized controls. 5-bromo-2-deoxyuridine pulse and pulse-chase experiments demonstrated that neither proliferation nor differentiation and survival of hippocampal progenitors were affected by sevoflurane exposure. In addition, behavioral testing of short- and long-term memory showed no differences between control and sevoflurane-exposed animals. Overall, these results suggest that brief sevoflurane exposure during critical periods of early postnatal development, although it does not seem to exert major long-term effects on brain circuitry development, can induce subtle changes in synaptic plasticity and spine density of which the physiological significance remains to be determined.
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Anesthesia, People's Hospital of Zhengzhou University, Zhengzhou 450000, China;
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology and Intensive Care, University Hospitals of Geneva, 1211 Geneva 4, Switzerland;
authors.forename: Timea
authors.initials: T
authors.lastname: Bodogan
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institute, Stockholm 171 77, Sweden;
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez-Galán
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou 450052, China;
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm 171 76, Sweden;
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden;
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institute, Stockholm 171 77, Sweden;
authors.forename: Guoxun
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm 171 76, Sweden;
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institute, Stockholm 171 77, Sweden; Department of Anesthesia, Surgical Services and Intensive Care, Karolinska University Hospital, Stockholm 171 76, Sweden; and.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Eriksson
authors.affiliation: Department of Anesthesiology and Intensive Care, University Hospitals of Geneva, 1211 Geneva 4, Switzerland;
authors.forename: Laszlo
authors.initials: L
authors.lastname: Vutskits
authors.affiliation: *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; niccolo.terrando@duke.edu.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Terrando
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: anesthesia; brain; memory; neurodevelopment; neurogenesis; neurotoxicity