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The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
08:47

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

Published on: November 19, 2008

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Peptidylarginine Deiminases as Drug Targets in Neonatal Hypoxic-Ischemic Encephalopathy

Sigrun Lange1

  • 1Department of Pharmacology, UCL School of Pharmacy, London, UK; Department of Biomedical Sciences, University of Westminster, London, UK.

Frontiers in Neurology
|March 5, 2016
PubMed

Insights

Novel factors like peptidylarginine deiminases (PADs) are key in perinatal brain injury from oxygen deprivation and infection. Inhibiting PADs shows neuroprotection in a neonatal hypoxic-ischemia model, offering new therapeutic avenues.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pathology

Background:

  • Perinatal brain injury, caused by oxygen deprivation and infection, leads to cerebral palsy and neurological disabilities.
  • Understanding the cellular mechanisms of white and gray matter damage is crucial for developing clinical interventions.

Purpose of the Study:

  • To identify novel factors involved in neonatal hypoxic-ischemia (HI) and infection-induced brain injury.
  • To investigate the role of calcium-regulated peptidylarginine deiminases (PADs) in mediating brain damage.
  • To evaluate the neuroprotective potential of pharmacological PAD inhibition.

Main Methods:

  • Utilized the Rice-Vannucci mouse model to simulate neonatal hypoxic-ischemia (HI).
  • Introduced lipopolysaccharide (LPS) to mimic synergistic infection alongside HI.
  • Administered pharmacological inhibitors targeting PADs.

Main Results:

  • Highlighted novel roles for peptidylarginine deiminases (PADs) in brain injury following HI.
  • Demonstrated significant neuroprotective effects of PAD inhibition in the HI model.
  • Showed that PAD inhibition is effective even with synergistic infection (LPS stimulation).

Conclusions:

  • Peptidylarginine deiminases (PADs) are key mediators in neonatal brain injury.
  • Pharmacological inhibition of PADs offers a promising neuroprotective strategy.
  • Targeting PADs could be a viable clinical approach for preventing neurological disabilities.

Keywords:
NETosisdeimination/citrullinationepigeneticshypoxic–ischemic encephalopathymicrobiomemicrogliamicrovesiclespeptidylarginine deiminases

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