Editorial: New Insights into the Pathophysiology and Treatment of Neonatal Hypoxic–Ischemic Encephalopathy

New Insights into the Pathophysiology and Treatment of Neonatal Hypoxic–Ischemic Encephalopathy Neonatal hypoxic–ischemic encephalopathy (HIE) is one of the leading causes of death and disability-adjusted life years (DALYs) in term infants (1, 2). This research topic presents a collection of one original article and four reviews covering translational research in HIE, including the utilization of animal models to unravel the pathophysiology of the disease, with a special focus on the development of novel therapies and the optimization of therapeutic hypothermia, the standard treatment for HIE. In an elegant review, Davidson et al. addressed the utilization of therapeutic hypothermia for HIE. They discussed the evolution of hypoxic–ischemic brain damage and the optimal moment to start the hypothermic treatment, as well as the length and intensity of the intervention. The authors pointed out that, although hypothermia protocols are fairly close to optimal (starting within the first 6 h of life and continuing for 48–72 h), they are only partly effective, since the number needed to treat is currently of approximately eight patients. Therefore, they argued that additional enhancements may come from better detection of patients who could benefit from the therapy, and by determining the optimal rate of rewarming. Moreover, the authors examined the possibility of combining therapeutic hypothermia with other promising experimental therapies such as erythropoietin and cell transplantation. In this regard, a mini-review by Lange discussed the possibility of combining peptidylarginine deiminases (PADs) inhibition with therapeutic hypothermia to improve its results. PADs are responsible for posttranslational deimination, which impact structural and functional properties of proteins. Consequently, PADs have a role in different developmental processes, and their dysfunc-tion has been linked with many degenerative and inflammatory disorders. The author discussed the roles of PADs after a hypoxic–ischemic insult, including aspects such as epigenetics, phagoptosis, and autophagy, and commented on the possible therapeutic applications of selective or non-selective PAD inhibition for HIE. The review article by Rumajogee et al. summarized the etiology and pathophysiology of cerebral palsy, and then described the Rice-Vannucci model and 12 other rodent models of HIE, detailing the characteristics, advantages, and limitations of each one of them. The authors mentioned