Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia

IntroductionHypoxia significantly impairs cognitive function due to the brain’s high demand for oxygen. While emerging evidence suggests that vagus nerve stimulation (VNS) can enhance cognition, its effectiveness in mitigating behavioral and molecular impairments caused by hypoxia remains unknown. T...

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Main Authors: Birendra Sharma, Krysten A. Jones, Laura K. Olsen, Raquel J. Moore, Frances S. Curtner, Candice N. Hatcher-Solis
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Behavioral Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1555229/full
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author Birendra Sharma
Birendra Sharma
Krysten A. Jones
Krysten A. Jones
Laura K. Olsen
Laura K. Olsen
Raquel J. Moore
Raquel J. Moore
Frances S. Curtner
Frances S. Curtner
Candice N. Hatcher-Solis
author_facet Birendra Sharma
Birendra Sharma
Krysten A. Jones
Krysten A. Jones
Laura K. Olsen
Laura K. Olsen
Raquel J. Moore
Raquel J. Moore
Frances S. Curtner
Frances S. Curtner
Candice N. Hatcher-Solis
author_sort Birendra Sharma
collection DOAJ
description IntroductionHypoxia significantly impairs cognitive function due to the brain’s high demand for oxygen. While emerging evidence suggests that vagus nerve stimulation (VNS) can enhance cognition, its effectiveness in mitigating behavioral and molecular impairments caused by hypoxia remains unknown. This study investigated whether VNS could alleviate hypoxia-induced deficits in cognitive performance and neurotrophin expression in rats.MethodsHealthy male Sprague–Dawley rats were randomly assigned to three groups: sham, hypoxia, and VNS + hypoxia. VNS was delivered during hypoxia (8% oxygen) exposure using 100 μs biphasic pulses at 30 Hz and 0.8 mA. Cognition and performance were assessed by behavioral testing and hippocampal tissue was collected for molecular analysis. NGF and BDNF mRNA levels were measured by quantitative PCR, and protein expression was evaluated by immunohistochemistry.ResultsThe passive avoidance test (PAT) performance was significantly reduced by hypoxia exposure compared to the sham group, and administration of VNS during hypoxia ameliorated this impairment. Hypoxia significantly reduced NGF and BDNF mRNA levels in the hippocampus 24 h post-exposure. VNS restored NGF mRNA to sham levels and partially increased BDNF mRNA. Immunohistochemistry results showed VNS significantly restored NGF protein expression in the hippocampus, while BDNF levels remained unchanged.DiscussionThese findings suggest that VNS may serve as a promising intervention for cognitive impairments induced by hypoxia.
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spelling doaj-art-dc71f07f7b5646ad9108bcec59971f0f2025-08-20T03:24:34ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532025-06-011910.3389/fnbeh.2025.15552291555229Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxiaBirendra Sharma0Birendra Sharma1Krysten A. Jones2Krysten A. Jones3Laura K. Olsen4Laura K. Olsen5Raquel J. Moore6Raquel J. Moore7Frances S. Curtner8Frances S. Curtner9Candice N. Hatcher-Solis10Air Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesOak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesAir Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesIntegrative Health & Performance Sciences, UES, Inc., Blue Halo, Dayton, OH, United StatesAir Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesOak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesAir Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesDCS Infoscitex, Dayton, OH, United StatesAir Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesDCS Infoscitex, Dayton, OH, United StatesAir Force Research Laboratory, Cognitive Neuroscience, 711th Human Performance Wing, Wright-Patterson AFB, OH, United StatesIntroductionHypoxia significantly impairs cognitive function due to the brain’s high demand for oxygen. While emerging evidence suggests that vagus nerve stimulation (VNS) can enhance cognition, its effectiveness in mitigating behavioral and molecular impairments caused by hypoxia remains unknown. This study investigated whether VNS could alleviate hypoxia-induced deficits in cognitive performance and neurotrophin expression in rats.MethodsHealthy male Sprague–Dawley rats were randomly assigned to three groups: sham, hypoxia, and VNS + hypoxia. VNS was delivered during hypoxia (8% oxygen) exposure using 100 μs biphasic pulses at 30 Hz and 0.8 mA. Cognition and performance were assessed by behavioral testing and hippocampal tissue was collected for molecular analysis. NGF and BDNF mRNA levels were measured by quantitative PCR, and protein expression was evaluated by immunohistochemistry.ResultsThe passive avoidance test (PAT) performance was significantly reduced by hypoxia exposure compared to the sham group, and administration of VNS during hypoxia ameliorated this impairment. Hypoxia significantly reduced NGF and BDNF mRNA levels in the hippocampus 24 h post-exposure. VNS restored NGF mRNA to sham levels and partially increased BDNF mRNA. Immunohistochemistry results showed VNS significantly restored NGF protein expression in the hippocampus, while BDNF levels remained unchanged.DiscussionThese findings suggest that VNS may serve as a promising intervention for cognitive impairments induced by hypoxia.https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1555229/fulllearningmemoryratsvagus nerve stimulationhypoxiaNGF
spellingShingle Birendra Sharma
Birendra Sharma
Krysten A. Jones
Krysten A. Jones
Laura K. Olsen
Laura K. Olsen
Raquel J. Moore
Raquel J. Moore
Frances S. Curtner
Frances S. Curtner
Candice N. Hatcher-Solis
Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
Frontiers in Behavioral Neuroscience
learning
memory
rats
vagus nerve stimulation
hypoxia
NGF
title Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
title_full Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
title_fullStr Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
title_full_unstemmed Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
title_short Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
title_sort vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia
topic learning
memory
rats
vagus nerve stimulation
hypoxia
NGF
url https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1555229/full
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