Targeted Pyroptosis with Resveratrol Nanoparticles to Reduce Secondary Brain Injury and Post-Traumatic Epilepsy

Traumatic brain injury (TBI) is associated with high mortality and disability rates globally, leading to significant sequelae, particularly post-traumatic epilepsy (PTE), which severely impacts physical health and quality of life. TBI involves primary and secondary damage, with the latter exacerbating the initial injury through neuroinflammation, influencing the overall outcome. Recent studies highlight pyroptosis as a crucial factor in the spread of secondary brain damage and the development of epilepsy, making it a vital therapeutic target. While current TBI treatments focus on surgical and medical interventions to reduce intracranial pressure, addressing secondary damage has limited clinical translation, largely due to the blood-brain barrier (BBB) hindering drug accumulation in the affected area. Resveratrol (RV) shows promise as a therapeutic agent due to its anti-inflammatory properties. This study presents a nanoliposome (C-Lips/RV) engineered with cysteine-alanine-glutamine-lysine peptides to enhance RV delivery to the brain, mitigate pyroptosis, and reduce inflammation. In TBI rats, C-Lips/RV demonstrates a longer half-life and effective targeting of brain injury, leading to reduced pyroptosis and PTE, slowed secondary damage progression, and improved functional recovery. This work offers insights into managing secondary brain damage and PTE.