Neurofunctional recovery effects of a Si-based agent in traumatic brain injury-induced chronic neuroinflammation

Traumatic brain injury (TBI) causes long-term cognitive and motor deficits driven partly by chronic neuroinflammation and oxidative stress. We evaluated whether an orally administered silicon (Si)-based antioxidant generating hydrogen in the intestine improves functional recovery after TBI. Male C57BL/6J mice were fed a 2.5% Si-based diet or control diet starting 1 week prior to controlled cortical impact (CCI) and subjected to CCI. The assigned diets were continuously administered for 1 week or 6 weeks after CCI. Behavioral outcomes were assessed using the Y-maze and open field tests at 1 and 6 weeks post-CCI. Histology, SV2A-PET imaging, systemic oxidative stress assays (d-ROMs and BAP), and brain qPCR for antioxidant-related genes were performed. At 1 week post-CCI, the Si group showed improved short-term memory in the Y-maze compared with controls. At 6 weeks post-CCI, locomotor activity was significantly higher in the Si group in the open field test. Microglial activation and SV2A-PET–derived synaptic density did not differ between groups. Systemic oxidative stress indices were similar; however, cortical and thalamic expression of Nrf2 pathway–related genes tended to be higher in the Si group at 6 weeks. In conclusion, oral administration of a Si-based agent improved short-term memory and locomotor function after CCI, potentially via localized antioxidant effects within the brain that support recovery of corticothalamic networks.