Browsing by Author "Brown, Candice M."

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    Assessment of Phase-Dependent Alterations in Cortical Glycolytic and Mitochondrial Metabolism Following Ischemic Stroke
    (Taylor & Francis, 2025) Rahimpour, Shokofeh; Meadows, Ethan; Hollander, John M.; Karelina, Kate; Brown, Candice M.; Anesthesia, School of Medicine
    Maintaining optimal brain metabolism supports neuronal function, synaptic communication, and cognitive processes. During ischemic stroke, brain metabolism and cellular bioenergetics within the neurovascular unit are disrupted, emphasizing the significance of understanding the physiology and pathology of the stroke brain. The objective of this study was to quantify and compare phase-dependent changes in glycolysis and oxidative phosphorylation following ischemic stroke by using the Seahorse XFe24 Analyzer. Since there are limited established methods to quantify glycolytic activity in brain tissue, we optimized the accuracy and reproducibility of extracellular acidification rate (ECAR) measurement by increasing the incubation time following exposure to each reagent. Following optimization, we quantified both ECAR and the oxygen consumption rate (OCR), a measure of oxidative phosphorylation, in cortical brain tissue punches corresponding to the penumbra from mice subjected to ischemic stroke. ECAR and OCR were quantified in tissue punches from the injured (ipsilateral) and the non-injured (contralateral) hemispheres at 48 hours, 7 days, and 14 days post-stroke. Normalized ECAR measurements showed elevated glycolytic activity in the ipsilateral and contralateral hemispheres at 7 days post-stroke compared to other time points. In contrast, normalized OCR measurements showed a modest increase in basal respiration within the ipsilateral hemispheres between 48 hours and 14 days post-stroke. In summary, the results demonstrate that ischemic stroke results in a distinct phase-dependent metabolic phenotype in both cortical hemispheres that persists up to 14 days after injury.
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    Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction
    (Sage, 2022-05-22) Nwafor, Divine C.; Brichacek, Allison L.; Foster, Chase H.; Lucke-Wold, Brandon P.; Ali, Ahsan; Colantonio, Mark A.; Brown, Candice M.; Qaiser, Rabia; Neurological Surgery, School of Medicine
    Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain’s vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.