Abstract
BACKGROUND: Therapeutic strategies for traumatic brain injury (TBI) in the last three decades have failed to show significant benefit in large scale studies. Given the multitude of pathological mechanisms involved in TBI, strategies focusing on multimodality regimen have gained interest as promising future interventions. HYPOTHESIS: We hypothesized that combining noninvasive transcranial magnetic stimulation (TMS) with rehabilitative training in an environmental enrichment (EE) can facilitate post-TBI recovery in rats via cortical excitability and reorganization. METHODS: We subjected rats to controlled cortical impact, and then assigned them to one of four groups: 1. No treatments (TBI), 2. EE after injury (TBI + EE), 3. TMS for one week (TBI + TMS), and 4. TMS for one week combined with EE (TBI + TMS/EE). For TMS, a 10 Hz repetitive TMS protocol was used. RESULTS: At 7 days, TBI + TMS and TBI + TMS/EE groups had significantly increased primary somatosensory cortex local field potential (LFP) compared to TBI and TBI + EE groups (P < 0.05). Also, TBI + TMS/EE group had significantly improved performance on beam walk test compared to TBI group (P < 0.005). At 6 weeks, there was significantly higher response in TBI + TMS/EE group compared to TBI + TMS for somatosensory cortex LFP (P < 0.05), bicep motor evoked potentials (MEP) (P < 0.05), challenge ladder test performance (P < 0.01), and fMRI responses to tactile forepaw stimulation. CONCLUSIONS: We demonstrate here for the first time the mechanism by which combined therapy using TMS and EE after TBI leads to functional improvement, possibly via cortical excitability and reorganization.