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

Perinatal hypoxic-ischemic(HI)brain injury is a leading cause of morbidity and longstanding disability in newborns(Millar et al.,2017).Improved neonatal intensive care has increased survival in infants with pregnancy and birth related complications.Nonetheless,many surviving neonates exhibit neurological abnormalities that can persist throughout life(Millar et al.,2017).Early neuroprotective strategies have the potential to improve neurological outcomes and attenuate developmental delay in neonates.However,hypothermia is the only currently approved intervention for HI encephalopathy in fullterm infants,which is only partially protective(Millar et al.,2017).Findings in preterm and full-term infants suggest that elevations in proinflammatory cytokines are important in the pathogenesis of HI-related brain injury(Millar et al.,2017).The high mobility group box-1(HMGB1),a representative damage associatedmolecular pattern(DAMP)protein,has been reported to be implicated in a variety of brain related inflammatory diseases including traumatic brain injury,epilepsy,and stroke(Nishibori et al.,2019).Anti-HMGB1 therapies have gained increasing interest to treat inflammation related disorders in the brain(Nishibori et al.,2019).However,there is a paucity of information regarding the pathology of HMGB1 in HI-related brain injury during the perinatal period.The current perspective discusses the potential contributions of HMGB1 to HI-related brain injury during the perinatal period and also addresses the potential of HMGB1 as a therapeutic target of the brain injury.Furthermore,this perspective emphasizes the potential for combinational therapeutics for hypothermia with anti-HMGB1 monoclonal antibodies(mAb)in perinatal HI brain injury.