British journal of anaesthesia
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Anaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction. ⋯ These data suggest that CoQ 10 reduces sevoflurane-induced cognitive deficiency by mitigating sevoflurane-induced mitochondrial dysfunction, the reduction in adenosine triphosphate, and synaptic dysfunction. Coenzyme Q 10 could provide an approach to reduce the neurotoxicity of anaesthesia in the developing brain.
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Isoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. ⋯ A single isoflurane exposure to early post-natal mice caused a hippocampal-dependent memory deficit that was not prevented by pre-administration of TAT-Pep5, although TAT-Pep5, an inhibitor of p75NTR, has been shown to reduce isoflurane-induced apoptosis. These findings suggest that neuronal apoptosis is not requisite for the development of cognitive deficits in the adults attendant with neonatal anaesthetic exposure.
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Previous work suggests that anaesthesia and surgery amplify the pathology and cognitive impairment of animals made vulnerable via age or specific transgenes. We hypothesized that surgery under propofol anaesthesia, a widely used i.v. general anaesthetic, has minimal delayed cognitive and neuroinflammatory sequelae in a vulnerable mouse transgenic model. ⋯ Surgery in a vulnerable transgenic mouse under propofol anaesthesia was associated with minimal to no changes in short- and long-term behaviour and no changes in neuropathology. This suggests that propofol anaesthesia is associated with better cognitive outcomes in the aged, vulnerable brain compared with inhalation anaesthesia.