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

Abstract

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.