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Research Article
Yang Wang
Dalian Municipal Central Hospital
Corresponding Author
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Background: Connexin 43 is the most abundant connexin protein expressed in astrocytes. Our previous research found that sevoflurane-induced neurotoxicity was related to Cx43 via JNK/MAPK/Ap-1 signaling pathway. Cx43 functions through hemichannels (HCs) and gap junctions (GJs) and both of them could affect the homeostasis of central nervous system. Carbenoxolone (Cbx) is generally considered as a Cx43 hemichannel and gap junction inhibitor in traditional applications. Therefore, we hypothesized that preadministration of Cbx may attenuate sevoflurane-induced cognitive dysfunction.
Methods: Seven-day-old SD rats (P7) were exposed to 3% sevoflurane for 4 hours with or without Cbx pretreatment at a dose of 50 mg/kg. Levels of Bcl-2, Bax, Cx43 and caspase-3 positive cells in P8 rat’s hippocampus were examined using Western blotting and immunohistochemistry. Morris water maze was performed from P28 to P33 to test the cognitive function.
Results: Cx43 levels and caspase-3 positive cells in P7 rat hippocampus were increased 1 day after exposure to 3% sevoflurane for 4 h compared with control rats. Sevoflurane anesthesia decreased the expression of Bcl-2 and increased the expression of Bax in P8 rat’s hippocampus (P<0.05, n=5). Exposure to sevoflurane led to significant cognitive impairment from P28 to P33.All these defects could not be alleviated by pretreatment with Cbx.
Conclusions: These data suggested that Cbx could not improve sevoflurane-induced neurotoxicity by inhibiting Cx43 HCs in the developing brain.
Keywords
sevoflurane, Connexin43, Neurotoxicity , Carbenoxolone, Developing brain
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CURRENT STATUS: Under Review
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Posted 21 Jan, 2021
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Received 28 Feb, 2021
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Yang Wang
Dalian Municipal Central Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 21 Jan, 2021
No community comments so far
Reviews received
Received 28 Feb, 2021
Reviewers agreed
On 26 Feb, 2021
Reviewers invited
Invitations sent on 25 Feb, 2021
Editor assigned
On 25 Feb, 2021
Editor invited
On 19 Jan, 2021
Submission checks complete
On 19 Jan, 2021
First submitted
On 15 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Connexin 43 is the most abundant connexin protein expressed in astrocytes. Our previous research found that sevoflurane-induced neurotoxicity was related to Cx43 via JNK/MAPK/Ap-1 signaling pathway. Cx43 functions through hemichannels (HCs) and gap junctions (GJs) and both of them could affect the homeostasis of central nervous system. Carbenoxolone (Cbx) is generally considered as a Cx43 hemichannel and gap junction inhibitor in traditional applications. Therefore, we hypothesized that preadministration of Cbx may attenuate sevoflurane-induced cognitive dysfunction.
Methods: Seven-day-old SD rats (P7) were exposed to 3% sevoflurane for 4 hours with or without Cbx pretreatment at a dose of 50 mg/kg. Levels of Bcl-2, Bax, Cx43 and caspase-3 positive cells in P8 rat’s hippocampus were examined using Western blotting and immunohistochemistry. Morris water maze was performed from P28 to P33 to test the cognitive function.
Results: Cx43 levels and caspase-3 positive cells in P7 rat hippocampus were increased 1 day after exposure to 3% sevoflurane for 4 h compared with control rats. Sevoflurane anesthesia decreased the expression of Bcl-2 and increased the expression of Bax in P8 rat’s hippocampus (P<0.05, n=5). Exposure to sevoflurane led to significant cognitive impairment from P28 to P33.All these defects could not be alleviated by pretreatment with Cbx.
Conclusions: These data suggested that Cbx could not improve sevoflurane-induced neurotoxicity by inhibiting Cx43 HCs in the developing brain.
Figure 1
Figure 2
Figure 3
Figure 4
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