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Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals

Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining le...

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Autores principales: Jimenez-Tellez, Nerea, Pehar, Marcus, Iqbal, Fahad, Casas-Ortiz, Alberto, Rice, Tiffany, Syed, Naweed I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953733/
https://www.ncbi.nlm.nih.gov/pubmed/36830927
http://dx.doi.org/10.3390/biomedicines11020391
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author Jimenez-Tellez, Nerea
Pehar, Marcus
Iqbal, Fahad
Casas-Ortiz, Alberto
Rice, Tiffany
Syed, Naweed I.
author_facet Jimenez-Tellez, Nerea
Pehar, Marcus
Iqbal, Fahad
Casas-Ortiz, Alberto
Rice, Tiffany
Syed, Naweed I.
author_sort Jimenez-Tellez, Nerea
collection PubMed
description Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining learning and memory in freely behaving animals, and in vitro using cultured neurons to assess its impact on viability, mitochondrial structure, and function. We demonstrate here that neonatal exposure to sub-clinically used concentrations of SEV results in significant, albeit subtle and previously unreported, learning and memory deficits in adult animals. These deficits involve neuronal cell death, as observed in cell culture, and are likely mediated through perturbed mitochondrial structure and function. Parenthetically, both behavioural deficits and cell death were prevented when the animals and cultured neurons were pre-treated with the anesthetic adjuvant Dexmedetomidine (DEX). Taken together, our data provide direct evidence for sevoflurane-induced cytotoxic effects at the neuronal level while perturbing learning and memory at the behavioural level. In addition, our data underscore the importance of adjuvant agents such as DEX that could potentially counter the harmful effects of commonly used anesthetic agents for better clinical outcomes.
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spelling pubmed-99537332023-02-25 Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals Jimenez-Tellez, Nerea Pehar, Marcus Iqbal, Fahad Casas-Ortiz, Alberto Rice, Tiffany Syed, Naweed I. Biomedicines Article Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)—both in vivo by examining learning and memory in freely behaving animals, and in vitro using cultured neurons to assess its impact on viability, mitochondrial structure, and function. We demonstrate here that neonatal exposure to sub-clinically used concentrations of SEV results in significant, albeit subtle and previously unreported, learning and memory deficits in adult animals. These deficits involve neuronal cell death, as observed in cell culture, and are likely mediated through perturbed mitochondrial structure and function. Parenthetically, both behavioural deficits and cell death were prevented when the animals and cultured neurons were pre-treated with the anesthetic adjuvant Dexmedetomidine (DEX). Taken together, our data provide direct evidence for sevoflurane-induced cytotoxic effects at the neuronal level while perturbing learning and memory at the behavioural level. In addition, our data underscore the importance of adjuvant agents such as DEX that could potentially counter the harmful effects of commonly used anesthetic agents for better clinical outcomes. MDPI 2023-01-28 /pmc/articles/PMC9953733/ /pubmed/36830927 http://dx.doi.org/10.3390/biomedicines11020391 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jimenez-Tellez, Nerea
Pehar, Marcus
Iqbal, Fahad
Casas-Ortiz, Alberto
Rice, Tiffany
Syed, Naweed I.
Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title_full Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title_fullStr Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title_full_unstemmed Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title_short Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals
title_sort dexmedetomidine pre-treatment of neonatal rats prevents sevoflurane-induced deficits in learning and memory in the adult animals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953733/
https://www.ncbi.nlm.nih.gov/pubmed/36830927
http://dx.doi.org/10.3390/biomedicines11020391
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