Transcranial direct current stimulation combined with amantadine in repetitive mild traumatic brain injury in rats

BACKGROUND: Balance and memory deficits are common in patients with repetitive mild traumatic brain injury (mTBI). OBJECTIVE: To investigate the combined effects of amantadine and transcranial direct current stimulation (tDCS) on balance and memory in repetitive mTBI rat models. METHODS: In this prospective animal study, 40 repetitive mTBI rats were randomly assigned to four groups: tDCS, amantadine, combination of amantadine and anodal tDCS, and control. The tDCS group received four sessions of anodal tDCS for four consecutive days. The amantadine group received four intraperitoneal injections of amantadine for four consecutive days. The combination group received four intraperitoneal injections of amantadine and anodal tDCS for four consecutive days. Motor-evoked potential (MEP), rotarod test, and novel object test results were evaluated before mTBI, before treatment, and after treatment. RESULTS: All groups showed significant improvements in the rotarod and novel object tests, particularly the combination group. The combination group showed a significant improvements in duration (p < 0.01) and maximal speed in the rotarod test (p < 0.01), as well as an improvement in novel object ratio (p = 0.05) and MEP amplitude (p = 0.05) after treatment. The combination group exhibited a significant increase in novel object ratio compared to the tDCS group (p = 0.04). The GFAP integral intensity of the left motor cortex and hippocampus was the lowest in the combination group. CONCLUSION: Combination treatment with amantadine and tDCS had positive effects on balance and memory recovery after repetitive mTBI in rats. Therefore, we expect that the combination of amantadine and tDCS may be a treatment option for patients with repetitive mTBIs.