Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The N...

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Main Authors: Inja Cho, Bon-Nyeo Koo, So Yeon Kim, Sujung Park, Eun Jung Kim, Eun Hee Kam, Jeongmin Kim
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/15/8806
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author Inja Cho
Bon-Nyeo Koo
So Yeon Kim
Sujung Park
Eun Jung Kim
Eun Hee Kam
Jeongmin Kim
author_facet Inja Cho
Bon-Nyeo Koo
So Yeon Kim
Sujung Park
Eun Jung Kim
Eun Hee Kam
Jeongmin Kim
author_sort Inja Cho
collection DOAJ
description Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.
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spelling doaj.art-24285006140b4b5f8fcf358df803f0b02023-12-01T22:58:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315880610.3390/ijms23158806Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling PathwayInja Cho0Bon-Nyeo Koo1So Yeon Kim2Sujung Park3Eun Jung Kim4Eun Hee Kam5Jeongmin Kim6Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaDexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.https://www.mdpi.com/1422-0067/23/15/8806antioxidantdexmedetomidineinflammationNLRP3 inflammasomereactive oxygen speciespostoperative cognitive dysfunction
spellingShingle Inja Cho
Bon-Nyeo Koo
So Yeon Kim
Sujung Park
Eun Jung Kim
Eun Hee Kam
Jeongmin Kim
Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
International Journal of Molecular Sciences
antioxidant
dexmedetomidine
inflammation
NLRP3 inflammasome
reactive oxygen species
postoperative cognitive dysfunction
title Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
title_full Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
title_fullStr Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
title_full_unstemmed Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
title_short Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway
title_sort neuroprotective effect of dexmedetomidine against postoperative cognitive decline via nlrp3 inflammasome signaling pathway
topic antioxidant
dexmedetomidine
inflammation
NLRP3 inflammasome
reactive oxygen species
postoperative cognitive dysfunction
url https://www.mdpi.com/1422-0067/23/15/8806
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