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24.11.2020 | Original Article

Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice

verfasst von: Yulim Lee, Ann Misun Youn, Xianshu Ju, Jianchen Cui, Boohwi Hong, Sangwon Yun, Youngkwon Ko, Yoon Hee Kim, Jun Young Heo, Woosuk Chung

Erschienen in: Journal of Anesthesia | Ausgabe 1/2021

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Abstract

Purpose

Measuring the neurotoxic effects of multiple anesthetic exposures during neurodevelopment is complex due to the numerous factors that can affect the outcome. While we recently discovered that the interval between multiple sevoflurane exposures can affect the level of neurotoxicity, the significance of interval for other anesthetic agents is unknown. Thus, we evaluated the significance of dosing interval in the neurotoxic effects of multiple ketamine injections in postnatal day (PND) 17 mice.

Methods

PND17 mice of both sexes were intraperitoneally injected with ketamine (35 mg/kg) three times at short (2 h) or long (24 h) intervals. Changes in synaptic transmission were measured in hippocampal pyramidal neurons 5 days after the last injection, and behavioral changes were assessed at the age of 8 weeks. Values are presented as mean ± SD.

Results

Whereas short-interval ketamine injections enhanced excitatory synaptic transmission, as evidenced by an increased frequency of miniature excitatory postsynaptic currents (mEPSCs; ketamine, 0.09 ± 0.07 Hz; control, 0.06 ± 0.03 Hz), long-interval ketamine injections did not; instead, they decreased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs; ketamine, 47.72 ± 6.90 pA; control, 51.21 ± 7.65 pA,). However, only long-interval ketamine injections induced long-term changes in anxiety behavioral in the open-field test (decrease in center duration; ketamine, 400.1 ± 162.8 s; control, 613.3 ± 312.7 s).

Conclusions

Multiple ketamine injections induce interval-dependent, long-lasting synaptic changes and behavioral impairments. Future studies should carefully consider the dosing interval as a significant factor when studying the neurotoxic effects of multiple anesthetic exposures.

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Titel: Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice
verfasst von: Yulim Lee
Ann Misun Youn
Xianshu Ju
Jianchen Cui
Boohwi Hong
Sangwon Yun
Youngkwon Ko
Yoon Hee Kim
Jun Young Heo
Woosuk Chung
Publikationsdatum: 24.11.2020
Verlag: Springer Nature Singapore
Erschienen in: Journal of Anesthesia / Ausgabe 1/2021
Print ISSN: 0913-8668
Elektronische ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-020-02876-7

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Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice