439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats

OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birt...

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Main Authors: Melanie Gail Wiley, Catrina Sims-Robinson, Heather A. Boger, Dorothea D. Jenkins, Mark S. George, Ralph H. Johnson
Format: Article
Language:English
Published: Cambridge University Press 2022-04-01
Series:Journal of Clinical and Translational Science
Online Access:https://www.cambridge.org/core/product/identifier/S2059866122002564/type/journal_article
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author Melanie Gail Wiley
Catrina Sims-Robinson
Heather A. Boger
Dorothea D. Jenkins
Mark S. George
Ralph H. Johnson
author_facet Melanie Gail Wiley
Catrina Sims-Robinson
Heather A. Boger
Dorothea D. Jenkins
Mark S. George
Ralph H. Johnson
author_sort Melanie Gail Wiley
collection DOAJ
description OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.
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spelling doaj.art-3754ebeea07e47fca769ef6a309c53472023-03-10T07:53:49ZengCambridge University PressJournal of Clinical and Translational Science2059-86612022-04-016868610.1017/cts.2022.256439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn ratsMelanie Gail Wiley0Catrina Sims-Robinson1Heather A. Boger2Dorothea D. Jenkins3Mark S. George4Ralph H. Johnson5Medical University of South CarolinaNeurosciences Department Neurology DepartmentNeurosciences DepartmentDepartment of PediatricsDepartment of Psychiatry and Behavioral Sciences Medical University of South Carolina, VA Medical CenterMedical University of South Carolina, VA Medical CenterOBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.https://www.cambridge.org/core/product/identifier/S2059866122002564/type/journal_article
spellingShingle Melanie Gail Wiley
Catrina Sims-Robinson
Heather A. Boger
Dorothea D. Jenkins
Mark S. George
Ralph H. Johnson
439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
Journal of Clinical and Translational Science
title 439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
title_full 439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
title_fullStr 439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
title_full_unstemmed 439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
title_short 439 The effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on hypoxic-ischemic injury in newborn rats
title_sort 439 the effect of non invasive transcutaneous auricular vagus nerve stimulation tavns on hypoxic ischemic injury in newborn rats
url https://www.cambridge.org/core/product/identifier/S2059866122002564/type/journal_article
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