Impact of anaesthetics and surgery on neurodevelopment: an update

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Impact of anaesthetics and surgery on neurodevelopment: an update R.D. Sanders, J. Hassell, A.J. Davidson, N.J. Robertson, D. Ma British Journal of Anaesthesia Volume 110, Pages i53-i72 (June 2013) DOI: 10.1093/bja/aet054 Copyright © 2013 The Author(s) Terms and Conditions

Fig 1 Proposed mechanisms of anaesthetic-induced neurodegeneration in the newborn involving the intrinsic and extrinsic apoptotic cell death pathways. Suppression of synaptic signalling is proposed to attenuate neurotrophic survival signals leading to activation of the intrinsic apoptotic cascade. This involves mobilization of the pro-apopotic protein Bax, which in turn induces cytochrome c (Cyto. C) release from mitochondria, activation of caspase-9, and subsequent induction of caspase 3 cleavage to provoke apoptosis. Anti-apoptotic effectors such as Bcl oppose this pathway. The extrinsic pathway is stimulated by ligands binding to death receptors located on the cell membrane that cause caspase 8 activation, which then cleaves and activates caspase 3. These ligands include cytokines such as TNF-α. British Journal of Anaesthesia 2013 110, i53-i72DOI: (10.1093/bja/aet054) Copyright © 2013 The Author(s) Terms and Conditions