High mobility group box-1 protein as a therapeutic target in perinatal hypoxic-ischemic brain injury

摘要

Perinatal hypoxic-ischemic(HI) brain injury isaleading cause ofmorbidity and long-standing disability in newborns (Millaretal., 2017). Improved neonatalintensivecare has increased survivalin infants with pregnancy and birth related complications. Nonetheless, many surviving neonates exhibit neurologicalabnormalities thatcan persist throughout life(Millaretal., 2017). Early neuroprotectivestrategies havethe potentialto improve neurological outcomesand attenuate developmental delay in neonates. However, hypothermiais the only currently approved intervention for HI encephalopathy in full-terminfants, which is only partially protective(Millaretal., 2017). Findings in pretermand full-terminfants suggest that elevations in pro-inflammatory cytokinesareimportant in the pathogenesis ofHI-related brain injury (Millaretal., 2017). The highmobility group box-1 (HMGB1),arepresentative damageassociated-molecular pattern (DAMP) protein, has been reported to beimplicated in a variety of brain related inflammatory diseases including traumatic brain injury,epilepsy,and stroke(Nishiborietal., 2019). Anti-HMGB1 therapies have gained increasing interest to treat inflammation related disorders in the brain (Nishiborietal., 2019). However, thereisa paucity ofinformation regarding the pathology ofHMGB1 inHI-related brain injury during the perinatal period. Thecurrent perspective discusses the potentialcontributions of HMGB1 to HI-related brain injury during the perinatal period and also addresses the potential ofHMGB1 asatherapeutictarget ofthe brain injury. Furthermore, this perspectiveemphasizes the potentialforcombinationaltherapeutics for hypothermia with anti-HMGB1 monoclonal antibodies (mAb) in perinatalHI brain injury.