Biology subjects

Cook, D. G.

Publications and source records attributed to Cook, D. G..

3 recordsLinked to original sources

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↗

bioRxiv2022

Timing matters: Sex differences in acute and chronic outcomes following repetitive blast mild traumatic brain injury

BackgroundRepetitive blast-related mild traumatic brain injury (mTBI) caused by exposure to high explosives is increasingly common among warfighters as well as civilians. While women have been serving in military positions with increased risk of blast exposure since 2016, there are few published reports examining sex as a biological variable in models of blast mTBI, greatly limiting diagnosis and treatment capabilities. As such, here we examined acute and chronic outcomes of repetitive blast trauma in female and male mice in relation to potential behavioral, inflammatory, microbiome, and vascular dysfunction. MethodsIn this study we utilized a well-established blast overpressure model to induce repetitive (3x) blast-mTBI in both female and male mice. Acutely following repetitive exposure, we measured serum and brain cytokine levels, blood-brain barrier (BBB) disruption, fecal microbial abundance, and locomotion and anxiety-like behavior in the open field assay. Chronically, in female and male mice we assessed behavioral correlates of mTBI and PTSD-related symptoms commonly reported by Veterans with a history of blast-mTBI using the elevated zero maze, acoustic startle, and conditioned odorant aversion paradigms. ResultsRepetitive blast exposure resulted in both similar and disparate patterns of acute serum and brain cytokine as well as gut microbiome changes in female and male mice. Acute BBB disruption following repetitive blast exposure was apparent in both sexes. While female and male blast mice both exhibited acute locomotor and anxiety-like deficits in the open field assay, only male mice exhibited chronic adverse behavioral outcomes. DiscussionRepresenting a novel survey of potential sex differences following repetitive blast trauma, our results demonstrate unique similar yet divergent patterns of blast-induced dysfunction in female vs. male mice and highlight novel targets for future diagnosis and therapeutic development.

neuroscience↗

bioRxiv2020

Blast-induced mild traumatic brain injury promotes comorbid stress responses elicited by environmental cues attending blast exposure

Repetitive mild traumatic brain injury (mTBI) has been called the "signature injury" of military Servicemembers in the Iraq and Afghanistan wars and is highly comorbid with posttraumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Preclinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction--but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD, here we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing upon well-established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that, even while anesthetized during blast exposure, environmental cues encountered in the peri-blast environment could be conditioned to evoke aversion/dysphoria and reexperiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, while both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure.

neuroscience↗