Project: Research project

Project Details


The mechanisms by which ischemia leads to neuronal injury within certain
"selectively vulnerable" regions of the central nervous system remain
incompletely understood. Within the past few years, a fresh perspective
has been cast on this problem by studies implicating neuronal activity in
the pathogenesis of ischemic brain injury. In this proposal, we seek to
establish the importance of altered levels of neuronal activity in
modulating ischemic injury within selectively vulnerable brain regions. We
shall employ well-characterized models of reversible focal and global
ischemia in the rat to investigate paradigms which entail the modulation of
local levels of functional and metabolic activity within the brain. Our
specific aims are to assess the role played by postischemic uncoupling of
local glucose utilization and blood flow in contributing to ischemic
injury; to determine whether stimulation of local brain metabolism by
functional activation of the vibrissal-barrel-field somatosensory pathway
in the peri-ischemic period affects the susceptibility of the barrel-field
region of neocortex to ischemia; and to discern whether neuronal death in
vulnerable areas is influenced by modifications of the local
neurotransmitter environment or by pharmacological modulation of local
levels of metabolic activity. A related aim represents, in effect, the
converse of the above: namely, to use the degree of local metabolic
responsivity to a standardized somatosensory activation stimulus as a
sensitive regional index of residual functional impairment following
transient ischemia. We shall employ a recently validated double-label
autoradiographic method to asess the quantitative topography of local brain
glucose metabolism, blood flow, and the metabolism/blood flow couple, and
shall correlate these observations with the results of regional energy
metabolite and neurotransmitter assay, and light-level and ultrastructural
morphology. It is intended that these studies will provide impetus to the
development of novel prophylactic or therapeutic strategies to protect the
brain during ischemia.
Effective start/end date8/1/857/31/93


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $272,708.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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