Electroacupuncture Prevents TBI-Induced Synaptic Loss by Inhibiting CaMKII/Drp1-Dependent Mitochondrial Fission

(1) Background: Traumatic brain injury (TBI) triggers synaptic loss, leading to long-term neurological deficits. 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.