L Tong1, M Cai1, Y Huang1, H Zhang1, B Su1, Z Li1, H Dong2. 1. Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China. 2. Department of Anesthesiology, Xijing Hospital, Xi'an, Shanxi 710032, China hldong6@hotmail.com.
Abstract
BACKGROUND: Preconditioning with volatile anaesthetic agents induces tolerance to focal cerebral ischaemia, although the underlying mechanisms have not been clearly defined. The present study analyses whether TREK-1, a two-pore domain K(+) channel and target for volatile anaesthetics, plays a role in mediating neuroprotection by sevoflurane. METHODS: Differentiated SH-SY5Y cells were preconditioning with sevoflurane and challenged by oxygen-glucose deprivation (OGD). Cell viability and expression of caspase-3 and TREK-1 were evaluated. Rats that were preconditioned with sevoflurane were subjected to middle cerebral artery occlusion (MCAO), and the expression of TREK-1 protein and mRNA was analysed. Neurological scores were evaluated and infarction volume was examined. RESULTS: Sevoflurane preconditioning reduced cell death in differentiated SH-SY5Y cells challenged by OGD. Sevoflurane preconditioning reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Sevoflurane preconditioning increased levels of TREK-1 mRNA and protein. Knockdown of TREK-1 significantly attenuated sevoflurane preconditioning-induced neuroprotective effects in vitro and in vivo. CONCLUSIONS: Sevoflurane preconditioning-induced neuroprotective effects against transient cerebral ischaemic injuries involve TREK-1 channels. These results suggest a novel mechanism for sevoflurane preconditioning-induced tolerance to focal cerebral ischaemia.
BACKGROUND: Preconditioning with volatile anaesthetic agents induces tolerance to focal cerebral ischaemia, although the underlying mechanisms have not been clearly defined. The present study analyses whether TREK-1, a two-pore domain K(+) channel and target for volatile anaesthetics, plays a role in mediating neuroprotection by sevoflurane. METHODS: Differentiated SH-SY5Y cells were preconditioning with sevoflurane and challenged by oxygen-glucose deprivation (OGD). Cell viability and expression of caspase-3 and TREK-1 were evaluated. Rats that were preconditioned with sevoflurane were subjected to middle cerebral artery occlusion (MCAO), and the expression of TREK-1 protein and mRNA was analysed. Neurological scores were evaluated and infarction volume was examined. RESULTS:Sevoflurane preconditioning reduced cell death in differentiated SH-SY5Y cells challenged by OGD. Sevoflurane preconditioning reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Sevoflurane preconditioning increased levels of TREK-1 mRNA and protein. Knockdown of TREK-1 significantly attenuated sevoflurane preconditioning-induced neuroprotective effects in vitro and in vivo. CONCLUSIONS:Sevoflurane preconditioning-induced neuroprotective effects against transient cerebral ischaemic injuries involve TREK-1 channels. These results suggest a novel mechanism for sevoflurane preconditioning-induced tolerance to focal cerebral ischaemia.
Authors: R Hata; G Mies; C Wiessner; K Fritze; D Hesselbarth; G Brinker; K A Hossmann Journal: J Cereb Blood Flow Metab Date: 1998-04 Impact factor: 6.200
Authors: Samuel Kamatham; Christopher M Waters; Andreas Schwingshackl; Salvatore Mancarella Journal: Pflugers Arch Date: 2019-09-12 Impact factor: 3.657