PERINATAL HYPOXIC ISCHEMIC BRAIN DAMAGE

Project: Research project

Description

The overall objective of the present Program Proposal is to improve our
understanding of the pathophysiologic mechanism leading to hypoxic-
ischemic damage in the human fetus and newborn infant and to develop
effective strategies to prevent or minimize permanent brain injury which
leads ultimately to mental retardation or developmental disability. Our
specific aims include: 1) to investigate underlying biochemical
mechanisms responsible for the occurrence of hypoxic-ischemic brain
damage in perinatal animals; 2) to study the evolution of alterations in
cerebral blood flow and metabolism which culminates in hypoxic-ischemia
brain damage; 3) to study the efficacy and mechanisms of action of
specific neuro-protective agents in preventing or reducing the severity
of perinatal hypoxic-ischemic brain damage; and 4) to ascertain whether
or not prolonged or repetitive seizure superimposed on cerebral hypoxia-
ischemic causes or accentuates the ultimate brain damage. All
experiments will be conducted in developing postnatal rats and newborn
dogs. Included in the Program Project Proposal are five basic research projects
and three Core projects, the latter two include an Administrative and
Biostatistics Core, Neuropathology Core, and MR Spectroscopy and Imaging
Core. The individual research project titles are: 1) Regional cerebral
blood flow and oxidative metabolism; 2) Free radical formation; 3) Energy
metabolism; 4) Hypothermic circulatory arrest; and 5) Status epilepticus.
Analytical techniques to be utilized include isotopic autoradiography,
spectrofluorometry, high pressure liquid chromatography, 31P MR
spectroscopy, MR imaging, light and electron microscopy. Scientific
disciplines represented in the Program Project are pediatric neurology,
perinatology, neuroradiology, neuropathology, neurochemistry, computer
science and biostatistics. It is anticipated that the findings derived from the described research
endeavors will have direct relevance to preventive and therapeutic
interventions necessary to reduce substantially the significance and
severity of mental retardation and development disability in developing
human infants and children.
StatusFinished
Effective start/end date9/6/9412/31/04

Funding

  • National Institutes of Health: $1,547,564.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Free Radicals
Iron
Brain Injuries
Neuroglia
Astrocytes
Oxidative Stress
Brain Hypoxia
Lipopolysaccharides
Nitric Oxide
Oligodendroglia
Brain Hypoxia-Ischemia
Iron-Regulatory Proteins
Wounds and Injuries
Brain
Superoxides
Cell Death
Energy Metabolism
Ischemia
Personal Autonomy
Nitric Oxide Synthase