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Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy

[Image: see text] Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotectiv...

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Autores principales: Zheng, XiaoYu, Li, WenYu, Xiang, Qian, Wang, YanXue, Qu, TingYu, Fang, Wei, Yang, HongNa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620906/
https://www.ncbi.nlm.nih.gov/pubmed/37929090
http://dx.doi.org/10.1021/acsomega.3c06250
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author Zheng, XiaoYu
Li, WenYu
Xiang, Qian
Wang, YanXue
Qu, TingYu
Fang, Wei
Yang, HongNa
author_facet Zheng, XiaoYu
Li, WenYu
Xiang, Qian
Wang, YanXue
Qu, TingYu
Fang, Wei
Yang, HongNa
author_sort Zheng, XiaoYu
collection PubMed
description [Image: see text] Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE.
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spelling pubmed-106209062023-11-03 Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy Zheng, XiaoYu Li, WenYu Xiang, Qian Wang, YanXue Qu, TingYu Fang, Wei Yang, HongNa ACS Omega [Image: see text] Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE. American Chemical Society 2023-10-16 /pmc/articles/PMC10620906/ /pubmed/37929090 http://dx.doi.org/10.1021/acsomega.3c06250 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Zheng, XiaoYu
Li, WenYu
Xiang, Qian
Wang, YanXue
Qu, TingYu
Fang, Wei
Yang, HongNa
Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title_full Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title_fullStr Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title_full_unstemmed Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title_short Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy
title_sort memantine attenuates cognitive and emotional dysfunction in mice with sepsis-associated encephalopathy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620906/
https://www.ncbi.nlm.nih.gov/pubmed/37929090
http://dx.doi.org/10.1021/acsomega.3c06250
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