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Anesthesiology

Inhibition of N-myc downstream-regulated gene-2 is involved in an astrocyte-specific neuroprotection induced by sevoflurane preconditioning.


PMID 24866406

Abstract

Mechanism of sevoflurane preconditioning-induced cerebral ischemic tolerance is unclear. This study investigates the role of N-myc downstream-regulated gene-2 (NDRG2) in the neuroprotection of sevoflurane preconditioning in ischemic model both in vivo and in vitro. At 2 h after sevoflurane (2%) preconditioning for 1 h, rats were subjected to middle cerebral artery occlusion for 120 min. Neurobehavioral scores (n = 10), infarct volumes (n = 10), cellular apoptosis (n = 6), and NDRG2 expression (n = 6) were determined at 24 h after reperfusion. In vitro, cultural astrocytes were exposed to oxygen-glucose deprivation for 4 h. Cellular viability, cytotoxicity, apoptosis, and NDRG2 expression (n = 6) were evaluated in the presence or absence of NDRG2-specific small interfering RNA or NDRG2 overexpression plasmid. Sevoflurane preconditioning decreased apoptosis (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling-positive cells reduced to 31.2 ± 5.3% and cleaved Caspase-3 reduced to 1.42 ± 0.21 fold) and inhibited NDRG2 expression (1.28 ± 0.15 fold) and nuclear translocation (2.21 ± 0.29 fold) in ischemic penumbra. Similar effects were observed in cultural astrocytes exposed to oxygen-glucose deprivation. NDRG2 knockdown by small interfering RNA attenuated oxygen-glucose deprivation-induced injury (cell viability increased to 80.5 ± 4.1%; lactate dehydrogenase release reduced to 30.5 ± 4.0%) and cellular apoptosis (cleaved Caspase-3 reduced to 1.55 ± 0.21 fold; terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling-positive cells reduced to 18.2 ± 4.3%), whereas NDRG2 overexpression reversed the protective effects of sevoflurane preconditioning. All the data are presented as mean ± SD. Sevoflurane preconditioning inhibits NDRG2 up-regulation and nuclear translocation in astrocytes to induce cerebral ischemic tolerance via antiapoptosis, which represents one new mechanism of sevoflurane preconditioning and provides a novel target for neuroprotection.

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T8877
2,3,5-Triphenyltetrazolium chloride, ≥95%
C19H15ClN4