4.6 Article

Single sevoflurane exposure decreases neuronal nitric oxide synthase levels in the hippocampus of developing rats

Journal

BRITISH JOURNAL OF ANAESTHESIA
Volume 109, Issue 2, Pages 225-233

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bja/aes121

Keywords

anaesthetic; sevoflurane; caspase 3; hippocampus; memory; neuronal nitric oxide synthase; sevoflurane

Categories

Funding

  1. National Science Foundation Council of China [81070995, 31171290, 31140050]
  2. Guangdong Science Foundation [2010B031600037]
  3. National Institutes of Health
  4. National Institute on Alcohol Abuse and Alcoholism, USA [AA016964, AA016618]

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The use of general anaesthetics in young children and infants has raised concerns regarding the adverse effects of these drugs on brain development. Sevoflurane might have harmful effects on the developing brain; however, these effects have not been well investigated. Postnatal day 7 (P7) SpragueDawley rats were continuously exposed to 2.3 sevoflurane for 6 h. We used the Fox battery test and Morris water maze (MWM) to examine subsequent neurobehavioural performance. Cleaved caspase-3 and neuronal nitric oxide synthase (nNOS) were quantified by immunoblotting, and the Nissl staining was used to observe the histopathological changes in the hippocampus. A single 6 h sevoflurane exposure at P7 rats resulted in increased cleaved caspase-3 expression and decreased nNOS levels in the hippocampus, and induced the loss of pyramidal neurones in the CA1 and CA3 subfields of the hippocampus at P78. These changes were accompanied by temporal retardation of sensorimotor reflexes. However, neither the Fox battery test at P121 nor the MWM test at P2832 showed differences between the air- and sevoflurane-treated groups. Although early exposure to sevoflurane increases activated caspase-3 expression and neuronal loss and decreases nNOS in the neonatal hippocampus, it does not affect subsequent neurobehavioural performances in juvenile rats.

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