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BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats

Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-...

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Autores principales: Jia, Danting, Wang, Fang, Bai, Zhixia, Chen, Xuexin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603093/
https://www.ncbi.nlm.nih.gov/pubmed/37884604
http://dx.doi.org/10.1038/s41598-023-45572-8
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author Jia, Danting
Wang, Fang
Bai, Zhixia
Chen, Xuexin
author_facet Jia, Danting
Wang, Fang
Bai, Zhixia
Chen, Xuexin
author_sort Jia, Danting
collection PubMed
description Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by LE rescues BPV induced neurotoxicity in hippocampal neurons in rats. Seven- to nine-day-old primary cultured hippocampal neurons were randomly divided into 6 groups: the blank control group (Ctrl), the bupivacaine group (BPV), the lipid emulsion group (LE), the bupivacaine + lipid emulsion group (BPV + LE), the bupivacaine + lipid emulsion + tyrosine kinase receptor B (TrkB) inhibitor group (BPV + LE + K252a), the bupivacaine + lipid emulsion + p75 neurotrophic factor receptor (p75(NTR)) inhibitor group (BPV + LE + TAT-Pep5). All hippocampal neurons were incubated for 24 h, and their growth state was observed by light microscopy. The relative TrkB and p75(NTR) mRNA levels were detected by real-time PCR. The protein expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, TrkB, p75(NTR) and cleaved caspase-3 were detected by western blotting. The results showed that primary hippocampal neuron activity was reduced by BPV. As administration of LE elevated hippocampal neuronal activity, morphology was also somewhat improved. The protein expression and mRNA levels of TrkB and p75(NTR) were decreased when BPV induced hippocampal neuronal toxicity, while the expression of BDNF was increased. At the same time, BPV increased the original generation of cleaved caspase-3 protein content by hippocampal neurons, while the content of cleaved caspase-3 protein in hippocampal neurons cotreated with LE and BPV was decreased. Thus, this study has revealed LE may reduce apoptosis and promote survival of hippocampal neurons by regulating the BDNF-TrkB pathway and the proBDNF-p75(NTR) pathway to rescue BPV induced central neurotoxicity in rats.
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spelling pubmed-106030932023-10-28 BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats Jia, Danting Wang, Fang Bai, Zhixia Chen, Xuexin Sci Rep Article Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by LE rescues BPV induced neurotoxicity in hippocampal neurons in rats. Seven- to nine-day-old primary cultured hippocampal neurons were randomly divided into 6 groups: the blank control group (Ctrl), the bupivacaine group (BPV), the lipid emulsion group (LE), the bupivacaine + lipid emulsion group (BPV + LE), the bupivacaine + lipid emulsion + tyrosine kinase receptor B (TrkB) inhibitor group (BPV + LE + K252a), the bupivacaine + lipid emulsion + p75 neurotrophic factor receptor (p75(NTR)) inhibitor group (BPV + LE + TAT-Pep5). All hippocampal neurons were incubated for 24 h, and their growth state was observed by light microscopy. The relative TrkB and p75(NTR) mRNA levels were detected by real-time PCR. The protein expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, TrkB, p75(NTR) and cleaved caspase-3 were detected by western blotting. The results showed that primary hippocampal neuron activity was reduced by BPV. As administration of LE elevated hippocampal neuronal activity, morphology was also somewhat improved. The protein expression and mRNA levels of TrkB and p75(NTR) were decreased when BPV induced hippocampal neuronal toxicity, while the expression of BDNF was increased. At the same time, BPV increased the original generation of cleaved caspase-3 protein content by hippocampal neurons, while the content of cleaved caspase-3 protein in hippocampal neurons cotreated with LE and BPV was decreased. Thus, this study has revealed LE may reduce apoptosis and promote survival of hippocampal neurons by regulating the BDNF-TrkB pathway and the proBDNF-p75(NTR) pathway to rescue BPV induced central neurotoxicity in rats. Nature Publishing Group UK 2023-10-26 /pmc/articles/PMC10603093/ /pubmed/37884604 http://dx.doi.org/10.1038/s41598-023-45572-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jia, Danting
Wang, Fang
Bai, Zhixia
Chen, Xuexin
BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title_full BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title_fullStr BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title_full_unstemmed BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title_short BDNF-TrkB/proBDNF-p75(NTR) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
title_sort bdnf-trkb/probdnf-p75(ntr) pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603093/
https://www.ncbi.nlm.nih.gov/pubmed/37884604
http://dx.doi.org/10.1038/s41598-023-45572-8
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