Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice

Traumatic brain injury (TBI) is caused by acquired damage that includes cerebral edema after a mechanical injury and may cause cognitive impairment. We explored the role of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) and aquaporin-4 (AQP4) in the process of edema an...

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Main Authors: Ruixing He, Xiaotian Zhang, Cong Pang, Lihui Lin, Shaoxun Li, Luhao Jin, Lianshu Ding, Weijie Wang
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023092435
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author Ruixing He
Xiaotian Zhang
Cong Pang
Lihui Lin
Shaoxun Li
Luhao Jin
Lianshu Ding
Weijie Wang
author_facet Ruixing He
Xiaotian Zhang
Cong Pang
Lihui Lin
Shaoxun Li
Luhao Jin
Lianshu Ding
Weijie Wang
author_sort Ruixing He
collection DOAJ
description Traumatic brain injury (TBI) is caused by acquired damage that includes cerebral edema after a mechanical injury and may cause cognitive impairment. We explored the role of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) and aquaporin-4 (AQP4) in the process of edema and cognitive abilities after TBI in NOX2−/− and AQP4−/− mice by using the Morris water maze test (MWM), step-down test (STD), novel object recognition test (NOR) and western blotting. Knockout of NOX2 in mice decreased the AQP4 and reduce edema in the hippocampus and cortex after TBI in mice. Moreover, inhibiting AQP4 by 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) or genetic deletion of AQP4 could attenuate neurological deficits without changing reactive oxygen species (ROS) levels after TBI in mice. Taken together, we suspected that inhibiting NOX2 could improve cognitive abilities by modulating ROS levels, then affecting AQP4 levels and brain edema after in TBI mice. Our study demonstrated that NOX2 play a key role in decreasing edema in brain and improving cognitive abilities by modulating AQP4 after TBI.
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spelling doaj.art-d4734519d4dc4070bf7a566e87c6c6432023-12-02T07:04:59ZengElsevierHeliyon2405-84402023-11-01911e22035Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in miceRuixing He0Xiaotian Zhang1Cong Pang2Lihui Lin3Shaoxun Li4Luhao Jin5Lianshu Ding6Weijie Wang7Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, ChinaDepartment of Neurosurgery, Hongze District People's Hospital of Huai'an City, Huai'an, Jiangsu, 223300, ChinaDepartment of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, ChinaDepartment of Pharmacy, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, ChinaDepartment of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, ChinaDepartment of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, ChinaDepartment of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China; Corresponding author.Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China; Corresponding author. Beijing west road No. 6, Huaiyin district, Huai'an, 223300, China.Traumatic brain injury (TBI) is caused by acquired damage that includes cerebral edema after a mechanical injury and may cause cognitive impairment. We explored the role of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) and aquaporin-4 (AQP4) in the process of edema and cognitive abilities after TBI in NOX2−/− and AQP4−/− mice by using the Morris water maze test (MWM), step-down test (STD), novel object recognition test (NOR) and western blotting. Knockout of NOX2 in mice decreased the AQP4 and reduce edema in the hippocampus and cortex after TBI in mice. Moreover, inhibiting AQP4 by 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) or genetic deletion of AQP4 could attenuate neurological deficits without changing reactive oxygen species (ROS) levels after TBI in mice. Taken together, we suspected that inhibiting NOX2 could improve cognitive abilities by modulating ROS levels, then affecting AQP4 levels and brain edema after in TBI mice. Our study demonstrated that NOX2 play a key role in decreasing edema in brain and improving cognitive abilities by modulating AQP4 after TBI.http://www.sciencedirect.com/science/article/pii/S2405844023092435TBINOX2AQP4Brain edemaCognitive abilities
spellingShingle Ruixing He
Xiaotian Zhang
Cong Pang
Lihui Lin
Shaoxun Li
Luhao Jin
Lianshu Ding
Weijie Wang
Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
Heliyon
TBI
NOX2
AQP4
Brain edema
Cognitive abilities
title Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
title_full Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
title_fullStr Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
title_full_unstemmed Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
title_short Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice
title_sort inhibition of nadph oxidase 2 improves cognitive abilities by modulating aquaporin 4 after traumatic brain injury in mice
topic TBI
NOX2
AQP4
Brain edema
Cognitive abilities
url http://www.sciencedirect.com/science/article/pii/S2405844023092435
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