Resveratrol activates the SIRT1/PGC-1 pathway in mice to improve synaptic-related cognitive impairment after TBI.

Traumatic brain injury (TBI) is the most common form of craniocerebral injury. Post-TBI neurological impairment is often accompanied by cognitive dysfunction. The potential molecular mechanisms of post-TBI cognitive impairment are not well characterized. Resveratrol, a natural polyphenolic agent, has been shown to improve cognitive function in neurological disorders and aging models through its anti-inflammatory activity. However, whether it can affect synapses to improve cognitive function and the potential mechanisms are not clear. Synapse plays an important role in cognitive function, and synaptophysin(SYN) is one of the important factors involved in synapse formation. Sirtuin 1 (SIRT1) has a neuroprotective effect via its effect on various biological processes, such as inflammation, metabolism, apoptosis, and autophagy. The results of this research suggest that resveratrol increases synaptophysin by activating the SIRT1/PGC-1 pathway and improves post-TBI cognitive function. Use of SIRT1 inhibitor (EX-527) and agonist (SRT1720) in the mice experiments verified the effect and mechanism of action of resveratrol in improving cognitive function. Our study identifies potential therapeutic targets for post-TBI cognitive dysfunction.