Browsing by Author "Race, Nicholas S."

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    Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations
    (Nature Publishing Group, 2018-07-06) Garcia-Gonzalez, Daniel; Race, Nicholas S.; Voets, Natalie L.; Jenkins, Damian R.; Sotiropoulos, Stamatios N.; Acosta, Glen; Cruz-Haces, Marcela; Tang, Jonathan; Shi, Riyi; Jérusalem, Antoine; Medicine, School of Medicine
    Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions. To this end, experiments were carried out to analyse and correlate post-injury oxidative stress distribution with cognitive deficits on a live rat exposed to blast. A computational model of the rat head was developed from imaging data and validated against in vivo brain displacement measurements. The blast event was reconstructed in silico to provide mechanistic thresholds that best correlate with cognitive damage at the regional neuronal tissue level, irrespectively of the shape or size of the brain tissue types. This approach was leveraged on a human head model where the prediction of cognitive deficits was shown to correlate with literature findings. The mechanistic insights from this work were finally used to propose a novel protective device design roadmap and potential avenues for therapeutic innovations against blast traumatic brain injury.
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    Psychosocial impairment following mild blast-induced traumatic brain injury in rats
    (Elsevier, 2021) Race, Nicholas S.; Andrews, Katharine D.; Lungwitz, Elizabeth A.; Vega Alvarez, Sasha M.; Warner, Timothy R.; Acosta, Glen; Cao, Jiayue; Lu, Kun-Han; Liu, Zhongming; Dietrich, Amy D.; Majumdar, Sreeparna; Shekhar, Anantha; Truitt, William A.; Shi, Riyi; Anatomy, Cell Biology and Physiology, School of Medicine
    Traumatic brain injury (TBI) is associated with increased risk for mental health disorders, impacting post-injury quality of life and societal reintegration. TBI is also associated with deficits in psychosocial processing, defined as the cognitive integration of social and emotional behaviors, however little is known about how these deficits manifest and their contributions to post-TBI mental health. In this pre-clinical investigation using rats, a single mild blast TBI (mbTBI) induced impairment of psychosocial processing in the absence of confounding physical polytrauma, post-injury motor deficits, affective abnormalities, or deficits in non-social behavior. Impairment severity correlated with acute upregulations of a known oxidative stress metabolite, 3-hydroxypropylmercapturic acid (3-HPMA), in urine. Resting state fMRI alterations in the acute post-injury period implicated key brain regions known to regulate psychosocial behavior, including orbitofrontal cortex (OFC), which is congruent with our previous report of elevated acrolein, a marker of neurotrauma and 3-HPMA precursor, in this region following mbTBI. OFC of mbTBI-exposed rats demonstrated elevated mRNA expression of metabotropic glutamate receptors 1 and 5 (mGluR1/5) and injection of mGluR1/5-selective agonist in OFC of uninjured rats approximated mbTBI-induced psychosocial processing impairment, demonstrating a novel role for OFC in this psychosocial behavior. Furthermore, OFC may serve as a hotspot for TBI-induced disruption of psychosocial processing and subsequent mental health disorders.