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Electroacupuncture (EA) benefits neurological conditions, but its mechanisms after TBI remain unclear. (2) Methods: We used a controlled cortical impact (CCI) mouse model. Behavioral outcomes were assessed using the modified neurological severity score (mNSS), rotarod, Y-maze, and novel object recognition test (NORT). Synaptic morphology was examined by transmission electron microscopy (TEM). Energy metabolism was assessed using biochemical assays, and mitochondrial function was assessed using flow cytometry. Quantitative real-time PCR (qPCR) and Western blotting (WB) were used to examine the underlying molecular mechanisms. (3) Results: We found that EA ameliorates TBI-induced motor and cognitive impairments by preserving synaptic and mitochondrial integrity. EA-treated mice showed improvements in mNSS, rotarod, NORT, and Y-maze performance, along with preserved synaptic ultrastructure and mitochondrial function. CaMKII overexpression abolished EA-induced neuroprotection, identifying the CaMKII\/Drp1 axis as a key mediator. (4) Conclusions: Thus, EA limits TBI deficits by restraining CaMKII\/Drp1-driven mitochondrial fission and subsequent synaptic loss.<\/jats:p>","DOI":"10.3390\/biom16081169","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:46:16Z","timestamp":1786455976000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electroacupuncture Prevents TBI-Induced Synaptic Loss by Inhibiting CaMKII\/Drp1-Dependent Mitochondrial Fission"],"prefix":"10.3390","volume":"16","author":[{"given":"Sisi","family":"Zhao","sequence":"first","affiliation":[{"name":"Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxi","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feidan","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenge","family":"Liao","sequence":"additional","affiliation":[{"name":"Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunzhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eadw7425","DOI":"10.1126\/sciadv.adw7425","article-title":"Delivery of a fibrin-binding hemostatic polymer ameliorates neurovascular damage and neural tissue loss after traumatic brain injury","volume":"11","author":"Han","year":"2025","journal-title":"Sci. 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