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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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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. |
format | Online Article Text |
id | pubmed-10620906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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