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Br J Anaesth. 2019 Dec;123(6):818-826. doi: 10.1016/j.bja.2019.08.019. Epub 2019 Sep 28.

Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure.

Author information

1
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
2
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Neuroscience Graduate Program, Cincinnati, OH, USA.
3
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Anesthesiology, Shanghai Children's Hospital, Shanghai, China.
4
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
5
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Molecular, Cellular and Biochemical Pharmacology, Cincinnati, OH, USA.
6
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
7
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
8
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Neuroscience Graduate Program, Cincinnati, OH, USA; Department of Anesthesia, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. Electronic address: steve.danzer@cchmc.org.

Abstract

BACKGROUND:

Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be 'injured' and integrate abnormally into the brain.

METHODS:

The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later.

RESULTS:

The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37-1.5; P=0.010).

CONCLUSIONS:

A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.

KEYWORDS:

anesthetic neurotoxicity; dendrite; dendritic spine; dentate gyrus; isoflurane; neurogenesis

PMID:
31570162
DOI:
10.1016/j.bja.2019.08.019
[Indexed for MEDLINE]

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