Proteomic analysis identifying proteins relevant for treatment success following experimental neonatal inflammation-sensitized hypoxia-ischemia.

Abstract

Understanding the mechanisms of injury following neonatal hypoxic-ischemic encephalopathy (HIE) is a major goal in neonatal research. HIE can have severe effects on cognitive and motor development in newborns, including an increased risk of death. As the incidence is 10-20 times higher in low- and middle-income countries compared to developed countries, the interest in a therapy exists worldwide. Therapeutic hypothermia (HT) is the only effective treatment after HIE. However, TH is not universally effective, particularly in cases of inflammation-sensitized hypoxia-ischemia (HI); it provides limited benefit. To identify proteins that may contribute to the reduced efficacy of HT in the case of pre-HI inflammation sensitization, the proteomic profiles of animals subjected to HI and HT combined with lipopolysaccharide (LPS) were analyzed via liquid chromatography mass spectrometry (LC-MS/MS). We identified proteins that potentially support the efficacy of HT and those that prevent the success of the therapy in the neonatal rat model of inflammation-sensitized HI. This study represents a step forward in identifying proteins related to the efficacy of HT following inflammation-sensitized HI. Therapeutic hypothermia is the only available treatment for neonatal hypoxic-ischemic encephalopathy, but not effective in models of inflammation-sensitized hypoxic-ischemic brain injury. Using liquid chromatography mass spectrometry, we identified proteins possibly having an effect on the treatment success of therapeutic hypothermia following experimental inflammation-sensitized hypoxic-ischemic brain injury. This proteomic analysis reveals proteins as potential markers that could prevent or support the efficacy of therapeutic hypothermia in experimental neonatal inflammation-sensitized hypoxic-ischemic encephalopathy.