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Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats

BACKGROUND: Hemorrhagic shock induces the cognitive deficiency. Sevoflurane postconditioning has been documented to provide neuroprotection against ischemic–reperfusion injury by suppressing apoptosis. Mitochondrial permeability transition pore (mPTP) plays an important role in apoptosis, but it is...

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Autores principales: Zhang, Li, Huang, Li, Wang, Jingxian, Zhang, Muchun, Zhang, Ye, Hu, Xianwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955830/
https://www.ncbi.nlm.nih.gov/pubmed/31833229
http://dx.doi.org/10.1002/brb3.1501
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author Zhang, Li
Huang, Li
Wang, Jingxian
Zhang, Muchun
Zhang, Ye
Hu, Xianwen
author_facet Zhang, Li
Huang, Li
Wang, Jingxian
Zhang, Muchun
Zhang, Ye
Hu, Xianwen
author_sort Zhang, Li
collection PubMed
description BACKGROUND: Hemorrhagic shock induces the cognitive deficiency. Sevoflurane postconditioning has been documented to provide neuroprotection against ischemic–reperfusion injury by suppressing apoptosis. Mitochondrial permeability transition pore (mPTP) plays an important role in apoptosis, but it is unknown if the protective effect of sevoflurane postconditioning on hemorrhagic shock and resuscitation is associated with the change of mPTP opening. Hence, the aim of the study was to find out the precise mechanism of the sevoflurane postconditioning. METHODS: Sprague Dawley rats were subjected to hemorrhage shock for 60 min and then exposed to 2.4% sevoflurane for 30 min at the instant of reperfusion. Additionally, an opener (atractyloside) or an inhibitor (cyclosporine A) of mPTP was used in the animal model before sevoflurane postconditioning. Rats were randomly assigned into groups of Sham, Shock, Shock+Sevoflurane, Shock+Atractyloside, Shock+Sevoflurane+Atractyloside, Shock+Cyclosporin A, and Shock+Sevoflurane+Cyclosporin A treatment. Rat behavior was assessed for 5 days by Morris water maze 72 hr after surgery, and then hippocampus CA1 region was immunohistochemically stained. Brains were harvested 24 hr after surgery to detect the protein expression levels of Bcl‐2, Bax, and cytochrome C by Western blot, the changes of mPTP opening, and mitochondrial membrane potential (MMP). RESULTS: We found that sevoflurane postconditioning significantly improved rats' spatial learning and memory ability, down‐regulated the expression of Bax, cytochrome C, and caspase‐3, up‐regulated the expression of Bcl‐2, decreased the mPTP opening, and increased the MMP. The neuroprotective effect of sevoflurane postconditioning was abolished by atractyloside, but cyclosporin A played the similar protective role as sevoflurane postconditioning. CONCLUSION: These findings proved that sevoflurane postconditioning improved spatial learning and memory ability in hemorrhage shock and resuscitation rats, the mechanism of which may be related to block mPTP opening, increase MMP, and reduce neuron apoptosis in the hippocampus.
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spelling pubmed-69558302020-01-17 Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats Zhang, Li Huang, Li Wang, Jingxian Zhang, Muchun Zhang, Ye Hu, Xianwen Brain Behav Original Research BACKGROUND: Hemorrhagic shock induces the cognitive deficiency. Sevoflurane postconditioning has been documented to provide neuroprotection against ischemic–reperfusion injury by suppressing apoptosis. Mitochondrial permeability transition pore (mPTP) plays an important role in apoptosis, but it is unknown if the protective effect of sevoflurane postconditioning on hemorrhagic shock and resuscitation is associated with the change of mPTP opening. Hence, the aim of the study was to find out the precise mechanism of the sevoflurane postconditioning. METHODS: Sprague Dawley rats were subjected to hemorrhage shock for 60 min and then exposed to 2.4% sevoflurane for 30 min at the instant of reperfusion. Additionally, an opener (atractyloside) or an inhibitor (cyclosporine A) of mPTP was used in the animal model before sevoflurane postconditioning. Rats were randomly assigned into groups of Sham, Shock, Shock+Sevoflurane, Shock+Atractyloside, Shock+Sevoflurane+Atractyloside, Shock+Cyclosporin A, and Shock+Sevoflurane+Cyclosporin A treatment. Rat behavior was assessed for 5 days by Morris water maze 72 hr after surgery, and then hippocampus CA1 region was immunohistochemically stained. Brains were harvested 24 hr after surgery to detect the protein expression levels of Bcl‐2, Bax, and cytochrome C by Western blot, the changes of mPTP opening, and mitochondrial membrane potential (MMP). RESULTS: We found that sevoflurane postconditioning significantly improved rats' spatial learning and memory ability, down‐regulated the expression of Bax, cytochrome C, and caspase‐3, up‐regulated the expression of Bcl‐2, decreased the mPTP opening, and increased the MMP. The neuroprotective effect of sevoflurane postconditioning was abolished by atractyloside, but cyclosporin A played the similar protective role as sevoflurane postconditioning. CONCLUSION: These findings proved that sevoflurane postconditioning improved spatial learning and memory ability in hemorrhage shock and resuscitation rats, the mechanism of which may be related to block mPTP opening, increase MMP, and reduce neuron apoptosis in the hippocampus. John Wiley and Sons Inc. 2019-12-12 /pmc/articles/PMC6955830/ /pubmed/31833229 http://dx.doi.org/10.1002/brb3.1501 Text en © 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Zhang, Li
Huang, Li
Wang, Jingxian
Zhang, Muchun
Zhang, Ye
Hu, Xianwen
Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title_full Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title_fullStr Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title_full_unstemmed Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title_short Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
title_sort sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955830/
https://www.ncbi.nlm.nih.gov/pubmed/31833229
http://dx.doi.org/10.1002/brb3.1501
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