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A key contributor to secondary damage and impediments in the repair process is the unregulated activation of microglia, which triggers neuroinflammation. Emerging evidence highlights the therapeutic potential of transcranial pulsed current stimulation (tPCS) in mitigating neurological deficits. However, despite these promising neuroprotective effects, its role and exact mechanisms in TBI remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Herein, a mouse model of TBI was established, and daily 30\u2010min tPCS treatments were administered for five consecutive days. Subsequently, we conducted comprehensive assessments of neurological function, microglial activation status, and neuroplasticity in the treated subjects. Additionally, a co\u2010culture system of BV2 and HT22 cells was developed, using LPS to activate microglia, to explore potential neuroprotective mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that tPCS plays a crucial role in mitigating neuroinflammation and promoting neurological recovery following TBI. The underlying mechanism likely involves tPCS enhancing orexin\u2010A (OX\u2010A) expression, which subsequently suppresses the NF\u2010\u03baB pathway and promotes the expression of neurorepair\u2010related markers. In\u00a0vitro experiments further clarified these findings, demonstrating that OX\u2010A effectively inhibited LPS\u2010induced M1 microglial polarization and promoted a shift towards the M2 phenotype. Furthermore, OX\u2010A significantly reduced intracellular ROS production and microglia\u2010induced neuronal apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that tPCS regulates microglial phenotype via the OX\u2010A\/NF\u2010\u03baB pathway, thereby suppressing neuroinflammation and enhancing neuroplasticity. These results provide a new perspective for the rehabilitation of individuals with TBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70606","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:46:27Z","timestamp":1757313987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuroprotective Effects of Transcranial Pulsed Current Stimulation: Modulation of Microglial Polarization in Traumatic Brain Injury"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5908-0672","authenticated-orcid":false,"given":"Peng","family":"Yao","sequence":"first","affiliation":[{"name":"Affiliated Rehabilitation Hospital Jiang Xi Medical College, Nanchang University  Nanchang Jiangxi China"},{"name":"Rehabilitation Medicine Clinical Research Center of Jiangxi Province  Nanchang Jiangxi China"},{"name":"Key Laboratory of Jiangxi Provincial Health 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