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

Abstract 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, bu...

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Main Authors: Li Zhang, Li Huang, Jingxian Wang, Muchun Zhang, Ye Zhang, Xianwen Hu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Brain and Behavior
Subjects:
Online Access:https://doi.org/10.1002/brb3.1501
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author Li Zhang
Li Huang
Jingxian Wang
Muchun Zhang
Ye Zhang
Xianwen Hu
author_facet Li Zhang
Li Huang
Jingxian Wang
Muchun Zhang
Ye Zhang
Xianwen Hu
author_sort Li Zhang
collection DOAJ
description Abstract 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 doaj.art-fe43c8c1e9ed4e0b935c56c791a298f42022-12-21T23:42:34ZengWileyBrain and Behavior2162-32792020-01-01101n/an/a10.1002/brb3.1501Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation ratsLi Zhang0Li Huang1Jingxian Wang2Muchun Zhang3Ye Zhang4Xianwen Hu5Department of Anesthesiology and Perioperative Medicine The Second Hospital of Anhui Medical University Hefei ChinaDepartment of Anesthesiology Lu'an Hospital Affiliated to Anhui Medical University Lu'an ChinaDepartment of Anesthesiology Lu'an Hospital Affiliated to Anhui Medical University Lu'an ChinaDepartment of Anesthesiology and Perioperative Medicine The Second Hospital of Anhui Medical University Hefei ChinaDepartment of Anesthesiology and Perioperative Medicine The Second Hospital of Anhui Medical University Hefei ChinaDepartment of Anesthesiology and Perioperative Medicine The Second Hospital of Anhui Medical University Hefei ChinaAbstract 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.https://doi.org/10.1002/brb3.1501apoptosishemorrhagic shock and resuscitationmitochondrial membrane potentialmitochondrial permeability transition poresevoflurane postconditioningspatial learning and memory
spellingShingle Li Zhang
Li Huang
Jingxian Wang
Muchun Zhang
Ye Zhang
Xianwen Hu
Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats
Brain and Behavior
apoptosis
hemorrhagic shock and resuscitation
mitochondrial membrane potential
mitochondrial permeability transition pore
sevoflurane postconditioning
spatial learning and memory
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 apoptosis
hemorrhagic shock and resuscitation
mitochondrial membrane potential
mitochondrial permeability transition pore
sevoflurane postconditioning
spatial learning and memory
url https://doi.org/10.1002/brb3.1501
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