REGIONAL CEREBRAL BLOOD FLOW AND OXIDATIVE METABOLISM

  • Levison, Steven (PI)
  • Connor, James (PI)
  • vannucci, Susan (PI)
  • Vannucci, Robert (PI)
  • Vannucci, Robert (PI)
  • Palmer, Charles (PI)
  • Smith, Michael (PI)
  • Towfighi, Javad (PI)
  • Vannucci, Robert (PI)
  • Palmer, Charles (PI)
  • Smith, Michael (PI)
  • Towfighi, Javad (PI)
  • Palmer, Charles (PI)
  • Towfighi, Javad (PI)
  • Connor, James (PI)

Project Details

Description

The overall objective of the present research is to elucidate biochemical
and physiologic mechanisms responsible for perinatal hypoxic-ischemic
brain damage and to develop methods which will arrest or retard these
processes. Specific aims include: 1) to characterize the evolution of
the threshold lesions which arise from cerebral hypoxia-ischemia in the
immature rat and to determine whether or not a delayed neuronal necrosis
occurs, especially of the hippocampus; 2) to characterize those critical
cellular metabolic events which either precede or parallel the evolution
of identifiable lesions resulting from cerebral hypoxia-ischemia in the
immature rat: 3) to determine the influence of alterations in glucose and
lactate homeostasis on hypoxic-ischemic brain damage in the immature rat
and to identify those mechanisms whereby glucose exerts either a
beneficial or harmful effect on neuropathologic outcome; 4) to determine
the extent to which mild hypothermia ameliorates hypoxic-ischemic brain
damage in the immune rat; 5) to investigate the potential beneficial
effect of carbon dioxide on hypoxic-ischemic brain damage in the immature
rat and to determine the mechanism(s) whereby carbon dioxide is
protective; and 6) to investigate the presumed beneficial effects of
specific pharmacologic interventions on hypoxic ischemic brain damage,
such interventions to include specific calcium blockers, excitatory amino
acid receptor antagonists, pyruvate dehydrogenase activators, and nitric
oxide synthase inhibitors. To accomplish these goals, we plan to use the
following analytical techniques: 1) the iodo-[14C]-amphetamine technique
to measure regional cerebral blood flow; 2) modification of the 2-
deoxy[14C]-glucose technique to measure regional cerebral glucose
utilization; 3) in vivo analysis of glycolytic and Krebs cycle
intermediates and high-energy phosphate reserves in brain tissue; 4)
determination of cerebral energy utilization, intracellular pH and the
redox state of brain tissue on a global, regional and micro-regional
basis; 5) regional analysis of calcium and sodium uptake and turnover by
brain using autoradiography; 6) light and electron microscopic analysis
of brain specimens; 7) MR spectroscopy. Seven-day postnatal rats will
be subjected to unilateral common carotid artery occlusion combined with
exposure to 8% oxygen for varying intervals. During the course of and
following hypoxia-ischemia, the animals will be subjected to those
procedures necessary to measure regional cerebral blood flow and
metabolism as well as the evolution of the neuropathologic alterations.
Additional studies will investigate the regional cerebrovascular and
metabolic responses of hypoxic-ischemic immature rats subjects to 1)
hyperglycemia; 2) hypothermia, 3) carbon dioxide; and 4) therapeutic
interventions, including calcium channel blockers, pyruvate dehydrogenase
activators, excitatory amino acid receptor antagonists and nitric oxide
synthase inhibitors.
StatusFinished
Effective start/end date1/1/0112/31/04

ASJC

  • Neuroscience(all)
  • Clinical Neurology
  • Neurology
  • Molecular Biology
  • Biochemistry
  • Spectroscopy
  • Radiology Nuclear Medicine and imaging
  • Biotechnology
  • Pediatrics, Perinatology, and Child Health
  • Cell Biology
  • Statistics and Probability
  • Pathology and Forensic Medicine
  • Organic Chemistry