Neonatology Fellow Loma Linda University Health San Bernadino, California, United States
Background: Necrotizing enterocolitis (NEC) is among the most common GI diseases in preterm neonates. VNS is often used to treat adult inflammatory diseases. VNS also has the potential to attenuate inflammation associated with NEC. However, VNS must first be studied pre-clinically to test its efficacy and safety. We hypothesize that non-invasive VNS will reduce the incidence and severity of NEC in a rat pup model. Objective: To determine if vagus nerve stimulation reduces GI inflammation in a rat model of necrotizing enterocolitis. Design/Methods: We will assign rat pups from 12 full-term litters (based on power analysis) into 6 treatment groups, with approximately 18-25 pups each: NEC induction with VNS, NEC induction with sham VNS, NEC induction with no VNS, no NEC induction with VNS, no NEC induction with sham VNS, and no NEC induction with no VNS. NEC induction pups will be separated from their mothers and receive an established NEC induction protocol. This includes administration of: hypertonic formula, lipopolysaccharide, and hypoxic/cooling stressing sessions. Non-NEC induction pups received normal newborn rat care with their mothers. VNS will be applied via microvascular clips gently attached to the pups’ earlobes for three, 30 minute sessions during the first 24 hours of life. Electrical stimulation will be constrained to 0.05 mA of current and 20 Hz frequency to stimulate the auricular branch of the vagus nerve. Pups who receive sham stimulation will have the ear clip electrodes applied without electrical stimulation.
We will immediately harvest GI tract samples from pups who die before 96 hours old. All surviving pups will be sacrificed and tissue harvested at 96 hours old. We will cryosection harvested tissue and score the GI sections (blinded) and assign a Bell NEC score of 0–4. The average NEC score for each treatment group will be calculated. NEC incidence will be defined as grades 2–4, and will be calculated for each treatment group. From this data set we will provide the first steps to determining whether VNS is an effective treatment for NEC in preterm infants.
