Microenvironment-responsive Hydrogel Reduces Seizures After Traumatic Brain Injury in Juvenile Rats by Reducing Oxidative Stress and Hippocampal Inflammation.

Traumatic brain injury (TBI) is the primary cause of child mortality and disability worldwide. It can result in severe complications that significantly impact children's quality of life, including post-traumatic epilepsy (PTE). An increasing number of studies suggest that TBI-induced oxidative stress and neuroinflammatory sequelae (especially inflammation in the hippocampus region) may lead to the development of PTE. Due to the blood-brain barrier (BBB), typical systemic pharmacological therapy for TBI cannot deliver berberine (BBR) to the targeted location in the early stages of the injury, although BBR has strong anti-inflammatory properties. To break through this limitation, we developed a microenvironment-responsive Gelatin methacrylate hydrogel (GM/PB) to deliver BBR for regulating neuroinflammatory reactions and removing ROS in the brain trauma microenvironment through poly(propylene sulfide) 60 (PPS 60 ). In situ injection of the GM/PB hydrogel efficiently bypassed the BBB and was administered directly to the surface of brain tissue. In post-traumatic brain injury models, GM/PB has the potential to mitigate oxidative stress and neuroinflammatory responses, facilitate functional recovery, and lessen seizing. These findings could lead to a new treatment for brain injuries that minimizes complications and improves the quality of life. This article is protected by copyright. All rights reserved.