RESEARCH PAPER
Effects of postnatal sevoflurane exposure on learning and memory in pre-adolescent rats
 
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1
Department of Anaesthesiology and Reanimation, City Hospital, Türkiye
 
2
Department of Biophysics, Faculty of Medicine, Ege University, Türkiye
 
3
Department of Biophysics, Faculty of Medicine, Akdeniz University, Türkiye
 
4
Department of Anaesthesiology and Reanimation, Faculty of Medicine, Akdeniz University, Türkiye
 
 
Corresponding author
Kübra Doğan Çelik   

Department of Anesthesiology and Reanimation, City Hospital, Türkiye
 
 
 
KEYWORDS
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ABSTRACT
Introduction and objective:
Sevoflurane, a commonly used inhalation anaesthetic in paediatric procedures, has been associated with cognitive impairments, particularly affecting learning and memory. Despite its widespread use, the mechanisms underlying its neurocognitive effects remain unclear. The aim of the study is to investigate the impact of sevoflurane exposure at various developmental stages and dosages on learning and memory in pre-adolescent rats.

Material and methods:
Ninety male Wistar rat pups were randomly assigned to six groups: Control, Sham, S1 (single dose on postnatal day 7 [P7]), S2 (repeated doses on P7, P8, P9), S3 (single dose on P21), and S4 (repeated doses on P21, P22, P23). Morris Water Maze (MWM) Test was performed to LTP was recorded to assess synaptic plasticity., while Open Field Test (OFT) was utilized to assess locomotor activity and anxiety-like behaviours. Long-term potentiation (LTP) recordings were performed to assess synaptic plasticity.

Results:
Sevoflurane exposure impaired learning and memory, with deficits most pronounced in the early exposure (S2) and repeated-dose (S2 and S4) groups. In the MWM, S2 showed significantly prolonged escape latency and reduced target-quadrant time, indicating impaired spatial memory.OFT revealed decreased locomotor activity and increased anxiety-like behaviours in S2, suggesting greater neurocognitive impairment following early developmental exposure and repeated dosing. LTP recordings demonstrated reduced fEPSP slopes and population spike (PS) amplitudes, particularly in S2 and repeated-dose groups, further supporting impaired synaptic plasticity, learning, and memory.

Conclusions:
Early-stage and repeated-dose sevoflurane exposure disrupts learning, memory, and locomotor activity, highlighting the importance of timing and dosage in paediatric anaesthesia.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the support from the Faculty of Medicine of Akdeniz University.
FUNDING
This work was funded by the Research Foundation of Akdeniz University, Turkey (Grant number: TTU-2021-5604).
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.
ETHICAL APPROVAL
The research protocols in this study were reviewed and approved by the Akdeniz University Local Ethics Committee for Experimental Animal Research (Approval No: 142, Date: August 10, 2020). All experimental procedures were conducted at the Akdeniz University Laboratory Animals Application and Research Center, in strict accordance with the international principles outlined in the Guide for the Care and Use of Laboratory Animals. Furthermore, to ensure transparency, reproducibility, and rigorous scientific reporting, the design and execution of the experiments, as well as the preparation of this manuscript, were performed in full compliance with the ARRIVE guidelines [14, 15]. The welfare of the animal subjects was monitored throughout the study to minimize pain, distress, and discomfort, adhering to institutional and regulatory ethical standards.
DATA AVAILABILITY
The raw data supporting the findings of this study are available from the corresponding author (Hanife Kabukçu, hanifekabukcu@akdeniz.edu.tr) upon reasonable request.
PEER REVIEW INFORMATION
Article has been screened for originality
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