Targeting high-mobility group box protein 1 (HMGB1) in pediatric traumatic brain injury: Chronic neuroinflammatory, behavioral, and epileptogenic consequences
Kyria M Webster, Sandy R Shultz, Ezgi Ozturk, Larissa K Dill, Mujun Sun, Pablo Casillas-Espinosa, Nigel C Jones, Peter J Crack, Terence J O'Brien, Bridgette D Semple
Experimental Neurology | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2019
High mobility group box protein-1 (HMGB1) has been implicated as a key mediator of neuroinflammation and neurodegeneration in a range of neurological conditions including traumatic brain injury (TBI) and epilepsy. To date, however, most studies have examined only acute outcomes, and the adult brain. We have recently demonstrated HMGB1 release after experimental TBI in the pediatric mouse. This study therefore examined the chronic consequences of acute HMGB1 inhibition in the same model, to test the hypothesis that HMGB1 is a pivotal mediator of neuropathological, neurobehavioral, and epilepsy outcomes in pediatric TBI. HMGB1 was inhibited by treatment with 50 mg/kg i.p. Glycyrrhizin (Gly), c..View full abstract
The authors acknowledge funding support from the National Health and Medical Research Council of Australia (NHMRC) in the form of Project Grants and Career Development Fellowships to BDS and SRS. The authors also thank the Biomedical Histology Facility at the University of Melbourne, and Monash Histology Platform, Monash University at the Alfred Hospital.