{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:21:43Z","timestamp":1787167303178,"version":"build-2736575974"},"reference-count":89,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Caffeine is a weak, nonselective adenosine receptor antagonist. At low-to-moderate doses, caffeine has a stimulating effect; however, at higher doses, it can act as a depressant. It can function both as a neuroprotectant and a neurotoxin. In experimental Traumatic Brain Injury (TBI), administration of this psychoactive drug has been associated with beneficial or detrimental effects, depending on the dose, model, and timing. In a healthy brain, caffeine can enhance alertness and promote wakefulness. However, its consumption during late adolescence and early adulthood disrupts normal pruning processes in the context of repetitive moderate TBI (mTBI), leading to changes in dendritic spine morphology, resulting in neurological and behavioral impairments. Caffeine can potentially reduce TBI-associated intracranial pressure, oxidative stress, lipid peroxidation, cytotoxic edema, inflammation, and apoptosis. It can enhance alertness and reduce mental fatigue, which is critical for the cognitive rehabilitation of TBI patients. Additionally, caffeine positively affects immune cells and aids recovery post-TBI. Antagonizing adenosine receptors involved in controlling synaptic transmission, synaptic plasticity, and synapse toxicity can improve cognitive function. Conversely, studies have also shown that caffeine consumers report significantly higher somatic discomfort compared to non-consumers. This review aims to explore various studies and thoroughly examine the positive and negative roles of caffeine in TBI.<\/jats:p>","DOI":"10.3390\/nu17111925","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T03:57:34Z","timestamp":1749009454000},"page":"1925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Caffeine: A Neuroprotectant and Neurotoxin in Traumatic Brain Injury (TBI)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8477-6225","authenticated-orcid":false,"given":"Bharti","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Surgery, NYC Health and Hospitals\u2014Elmhurst, New York, NY 11373, USA"},{"name":"Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, 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