Background <p>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.</p> Methods <p>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).</p> Results <p>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.</p> Conclusion <p>This study represents a step forward in identifying proteins related to the efficacy of HT following inflammation-sensitized HI.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Therapeutic hypothermia is the only available treatment for neonatal hypoxic-ischemic encephalopathy, but not effective in models of inflammation-sensitized hypoxic-ischemic brain injury.</p> </ItemContent> <ItemContent> <p>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.</p> </ItemContent> <ItemContent> <p>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.</p> </ItemContent> </UnorderedList></p>

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

  • Hannah Burkard,
  • Damjan Osredkar,
  • Elke Maes,
  • Maria E. Bernis,
  • Anna-Sophie Bremer,
  • Margit Zweyer,
  • Paul Dowling,
  • Kay Ohlendieck,
  • Marianne Thoresen,
  • Hemmen Sabir

摘要

Background

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.

Methods

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).

Results

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.

Conclusion

This study represents a step forward in identifying proteins related to the efficacy of HT following inflammation-sensitized HI.

Impact

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.