New Therapeutic Paradigms in Neonatal Hypoxic-Ischemic Encephalopathy

In neonates with hypoxic-ischemic encephalopathy (HIE), neuroprotection mediated by therapeutic hypothermia (TH) is the standard of care in developed nations; however TH may be not beneficial or contraindicated in developing world. Moreover, in most of the clinical trials, hypothermic neuroprotection was incomplete because many infants still die or suffer significant neurological sequelae. Therefore, finding innovative, neuroprotective compounds for this encephalopathy represents an important and urgent need. In reference to the recent review by Zhou et al., ACS Chem. Neurosci. 2023 14, 1-9, in this viewpoint, we discuss the therapeutic role of ketone bodies and thiamine in neonatal HIE, their possible synergistic effect, and how these micronutrients may provide additive neuroprotection to TH and improve safer and effective treatment strategies also helpful in lowmiddle-income countries.