{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:14:24Z","timestamp":1793157264125,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) causes cortical dysfunction by increasing oxidative stress, neuroinflammation, apoptosis, and mitochondrial dysregulation, and impairing neurotrophic signaling and neurogenesis. This systematic review aimed to evaluate the effectiveness of exercise training on cortical molecular dysregulation and motor function in post-TBI. Following PRISMA 2020 guidelines, PubMed, EMBASE, and Web of Science were searched up to August 2025. Of 1173 records, 35 studies involving exercise training in post-TBI animal models were included. Exercise training protocols included voluntary wheel running, treadmill running, and swimming, with durations ranging from 7 to 63 days. Study quality was assessed using the CAMARADES checklist. Exercise training increased cortical glutathione and Na+\/K+-ATPase activity and reduced oxidative stress in post-TBI. It reduced microglial, astrocytic reactivity, and pro-inflammatory markers, including IL-1\u03b2 and TNF-\u03b1 expression in post-TBI. It also reduced caspase activity while increasing heat shock protein 20 (HSP20), thereby downregulating cortical apoptosis in post-TBI. It enhanced motor function, cortical neurogenesis, and neurotrophic factors signaling, including BDNF, in post-TBI. Exercise training improved motor function and cortical neuroprotection by reducing oxidative stress, neuroinflammation, and apoptosis, while enhancing neurotrophic signaling and neurogenesis in post-TBI rodents, but the regulation of let-7c, IL-6, and mitochondrial function remained unclear. (PROSPERO: CRD420251073725)<\/jats:p>","DOI":"10.3390\/ijms27010052","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:27:47Z","timestamp":1766500067000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cortical Neuroprotective Mechanisms of Exercise Training in Post-Traumatic Brain Injury: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6828-2993","authenticated-orcid":false,"given":"Farhan","family":"Yousaf","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 110122, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6674-125X","authenticated-orcid":false,"given":"Sean","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-2151","authenticated-orcid":false,"given":"Shahid","family":"Ishaq","sequence":"additional","affiliation":[{"name":"PhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung 110122, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-8349","authenticated-orcid":false,"given":"Shin-Da","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 110122, Taiwan"},{"name":"PhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung 110122, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Corrigan, F., Wee, I.C., and Collins-Praino, L.E. 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