• Grafe, Marjorie (PI)
  • Reese, T. (PI)

Project: Research project

Project Details


The objective of this research is to characterize the effects of perinatal
hypoxic/ischemic injury on brain development, with the long-term aims of
reducing the morbidity and mortality associated with this type of brain
injury. Perinatal hypoxic/ischemic brain injury occurs in both term and
preterm infants, and is a major cause of perinatal mortality, neonatal
morbidity, and long-term neurologic deficits. The morphological and
functional damage of perinatal ischemia is different from that in the adult
brain. Possible explanations for these differences include: variation in
the etiology of the hypoxia/ischemia, the developmental state of
susceptible cells, changes in the distribution of susceptible cells, or
differences in the cellular mechanisms of injury. The initial experiments in this proposal will determine the morphologic
effects of a focal hypoxic/ischemic injury on the developing brain at a
range of ages and severity of injury, using unilateral carotid occlusion
and hypoxia in the neonatal rat. The effects of ischemic injury on
neurogenesis, cell migration, and neuronal differentiation, will be
examined using 3H-thymidine autoradiography and staining with the rapid
Golgi method. This model will then be used for study of the effects of
perinatal hypoxic/ischemic injury on learning behavior. Subsequent
experiments will examine the roles of the glutamate (NMDA) receptor in the
physical and behavioral deficits resulting from perinatal hypoxic/ischemic
brain injury, first by examining the developmental distribution of this
receptor in the immature rat and human brain, then by looking at the
effects of NMDA receptor antagonism. No reliable small animal model for global perinatal ischemia is currently
in use. Development of a global ischemia model to supplement the above
studies will be an important goal during the course of this proposal, as
much perinatal ischemic injury occurs or begins prior to birth.
Effective start/end date4/15/903/31/96


  • National Institutes of Health: $81,179.00
  • National Institutes of Health: $81,179.00


  • Medicine(all)
  • Neuroscience(all)


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