Targeted Pyroptosis\nwith Resveratrol Nanoparticles\nto Reduce Secondary Brain Injury and Post-Traumatic Epilepsy

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