摘要Neonatal hypoxic-ischemic encephalopathy is the leading cause of brain injury in term infants worldwide and disproportionately affects low-and middle-income communities.Therapeutic hypothermia,the standard of care for hypoxic-ischemic encephalopathy in high-resourced settings,has no effect on morbidity and increases mortality after hypoxic-ischemic encephalopathy in low-and middle-income settings.Intranasal administration offers the opportunity to deliver more accessible treatments for all babies with neonatal hypoxic-ischemic encephalopathy due to lower resource needs,ease of administration,and the capacity to directly target the brain.We reviewed preclinical literature concerning intranasal treatments for hypoxic-ischemic encephalopathy and developed a novel semi-quantitative index ranking intranasal therapies for their potential for further development as biologically plausible,effective,and accessible treatments for hypoxic-ischemic encephalopathy.We searched PubMed and Google Scholar for peer-reviewed articles on intranasal therapies for hypoxic-ischemic encephalopathy using the mesh phrases"Neonatal hypoxic-ischemic encephalopathy intranasal"and"Neonatal brain intranasal."Sixty-two studies were included that described thirty-four unique intranasal therapies.Neonatal intranasal therapies have been widely studied in small animal models,infrequently in large animals,and only recently in human clinical trials.Our semi-quantitative ranking revealed cell-based therapies as potentially the most effective and developed intranasal therapy in animal models of hypoxic-ischemic encephalopathy,though the pharmaceutical support compulsory to current cell-based treatments limits their accessibility in low-resourced settings.Intranasal therapies for neonatal hypoxic-ischemic encephalopathy have both feasibility and neuroprotective potential for safe,effective,and accessible treatment of hypoxic-ischemic encephalopathy.Additional research is needed for translation to humans.Future investigation should emphasize appropriate animal modeling with pharmaceutics and cells,combined with an evaluation of the brain connectome and neurobehavioral outcomes.