Abstract
ObjectiveThe mechanisms by which exposure of the late-stage progenitor cells to the anesthesia sevoflurane alters their differentiation are not known. We seek to query whether the effects of sevoflurane on late-stage progenitor cells might be regulated by apoptosis and/or autophagy.MethodsTo address the short-term impact of sevoflurane exposure on granule cell differentiation, we used 5-bromo-2-deoxyuridine (BrdU) to identify the labeled late-stage progenitor granule cells. Male or female rats were exposed to 3% sevoflurane for 4 h when the labeled granule cells were 2 weeks old. Differentiation of the BrdU-labeled granule cells was quantified 4 and 7 days after exposure by double immunofluorescence. The expression of apoptosis and autophagy in hippocampal dentate gyrus (DG) was determined by western blot and immunofluorescence. Western blot for the expression of NF-κB was used to evaluate the mechanism. Morris water maze (MWM) test was performed to detect cognitive function in the rats on postnatal 28–33 days.ResultsExposure to sevoflurane decreased the differentiation of the BrdU-labeled late-stage progenitor granule cells, but increased the expression of caspase-3, autophagy, and phosphorylated-P65 in the hippocampus of juvenile rats and resulted in cognitive deficiency. These damaging effects of sevoflurane could be mitigated by inhibitors of autophagy, apoptosis, and NF-κB. The increased apoptosis could be alleviated by pretreatment with the autophagy inhibitor 3-MA, and the increased autophagy and apoptosis could be reduced by pretreatment with NF-κB inhibitor BAY 11-7085.ConclusionThese findings suggest that a single, prolonged sevoflurane exposure could impair the differentiation of late-stage progenitor granule cells in hippocampal DG and cause cognitive deficits possibly via apoptosis activated by autophagy through NF-κB signaling. Our results do not preclude the possibility that the affected differentiation and functional deficits may be caused by depletion of the progenitors pool.
Highlights
Sevoflurane is widely used as the sole anesthetic agents in pediatric surgical procedures because it is less neurotoxic than other volatile anesthetics, such as isoflurane (Drobish et al, 2016; Liu et al, 2017; Murphy et al, 2017)
To investigate the mechanism of autophagy induced by IκB/NF-κB signaling after sevoflurane exposure, we examined the level of LC3B in the sevoflurane + BAY11-7085 group
These results indicated that delayed maturation of dentate gyrus (DG) cells by sevoflurane can be affected by NF-κB levels, supporting the findings that NF-κB inhibitor could promote the survival of neural stem cells and differentiation of neurons
Summary
Sevoflurane is widely used as the sole anesthetic agents in pediatric surgical procedures because it is less neurotoxic than other volatile anesthetics, such as isoflurane (Drobish et al, 2016; Liu et al, 2017; Murphy et al, 2017). Many basic and clinical studies have demonstrated that anesthetic neurotoxicity is determined by the stage of brain development at the time of exposure, the degree of anesthetic exposure, and regions of the brain (Hofacer et al, 2013; Qiu et al, 2016; McCann and de Graaff, 2017). In the basic rodent studies, neurotoxicity of GAs is widely measured within 14-day-old animals (Zhu et al, 2010). Hofacer et al (2013) suggest that certain brain regions, such as dentate gyrus (DG) of the hippocampus, may be affected by 1.5% isoflurane even beyond the first 14 days of rodent life. 14-day-old granule cells are vulnerable to cell death after anesthetic exposure in 21-day-old mice (Hofacer et al, 2013)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
