Schuessler, B. | Search bioRxiv

bioRxiv2026

Non-invasive Vagal Nerve Stimulation as a Potential Treatment for Repetitive Blast Trauma

BackgroundPolytrauma caused by exposure to high explosives (blast) is increasingly common among military personnel and civilians yet treatment for related post-concussive symptoms and chronic behavioral dysfunction is limited. Therapeutic targets following these injuries are typically focused on the central nervous system, with less attention placed on potentially more accessible peripheral targets. Vagus nerve stimulation (VNS) has recently gained traction as a potential therapeutic modality but has yet to be examined in a blast trauma setting. MethodsOur well-established blast overpressure model was utilized to induce repetitive (3x) blast trauma, followed by treatment with non-invasive transcutaneous VNS one hour following each blast exposure in male mice. Acutely following repetitive blast exposure, we measured serum and brain cytokine levels, fecal microbial abundance, and locomotion and anxiety-like behavior in the open field assay. Chronically (1-3 months post blast), mice were assessed for behavioral outcomes related to mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD), including acoustic startle (hyperreactivity), probabilistic discounting (risky decision making), and two-bottle choice test (voluntary alcohol consumption). ResultsVNS treatment following blast exposure decreased acute blast-induced inflammatory response in the blood and brain, especially serum IL-9 and IP-10, and brain MPC-1. Chronic behavior tests demonstrated a VNS-dependent reduction in blast-induced risky decision-making and a decreased intake and preference for ethanol. Conversely, VNS was not effective in preventing acute blast effects on the microbiome or chronic hyperreactivity behaviors measured with acoustic startle. DiscussionThis study identifies the vagus nerve as a novel peripheral target for treating acute and chronic blast-induced dysfunction.

neuroscience↗

bioRxiv2026

If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice

The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures. We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into pellets ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the pellets, and blood was collected to compare corticosterone levels relative to traditional gavage FMT. Plasma corticosterone levels were found to be significantly lower in mice receiving FMT via pellets compared to oral gavage. Furthermore, relative to gavage FMT, microbial signatures of mice receiving FMT via pellets were more similar to those of the donor pellets at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta-diversity distances. Together, these results establish effective antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.

microbiology↗