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Following traumatic brain injury, extracellular glutamate levels increase, contributing to excitotoxicity, circuit dysfunction, and morbidity. Increased neuronal glutamate release and compromised astrocyte-mediated uptake contribute to elevated glutamate, but the mechanistic and spatiotemporal underpinnings of these changes are not well established. Using the controlled cortical impact model of TBI and iGluSnFR glutamate imaging, we quantified extracellular glutamate dynamics after injury. Three days postinjury, glutamate release was increased, and glutamate uptake and GLT-1 expression were reduced. Seven and 14 days postinjury, glutamate dynamics were comparable between sham and controlled cortical impact animals. Changes in peak glutamate response were unique to specific cortical layers and proximity to injury. This was likely driven by increases in glutamate release, which was spatially heterogeneous, rather than reduced uptake, which was spatially uniform. The astrocyte K+ channel, Kir4.1, regulates activity-dependent slowing of glutamate uptake. Surprisingly, Kir4.1 was unchanged after controlled cortical impact and accordingly, activity-dependent slowing of glutamate uptake was unaltered. This dynamic glutamate dysregulation after traumatic brain injury underscores a brief period in which disrupted glutamate uptake may contribute to dysfunction and highlights a potential therapeutic window to restore glutamate homeostasis.<\/jats:p>","DOI":"10.1093\/cercor\/bhaf031","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T23:21:45Z","timestamp":1738106505000},"source":"Crossref","is-referenced-by-count":6,"title":["Glutamate uptake is transiently compromised in the perilesional cortex following controlled cortical impact"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-7729","authenticated-orcid":false,"given":"Jacqueline P","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Tufts University School of Medicine , Boston, MA ,","place":["United States"]},{"name":"Cellular, Molecular, and Developmental Biology Program, Tufts University School of Medicine , Boston, 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