Project Details


One of the critical determiners of oxygen delivery to brain is diffusion
from the vascular system. This is controlled by open capillary density,
surface area and diameter of the perfused capillary bed of all brain
regions. While regional blood flow, the other determiner, can easily be
measured, until now open capillary density and capillary reserves could not
be quantitatively determined regionally in brain. Our hypotheses are that
capillary reserves are one of the key unexplored mechanisms available to
different brain regions to protect them against 02 supply deficits and that
different regions have different reserves. To test these hypotheses, we
have developed a new method to determine perfused and total capillary
density on a regional basis in brain. A fluorescent dye is injected into
the vein of a rat. After an appropriate time, the head is removed and
quick-frozen. Photomicrographs of thin sections of various brain regions
are obtained, where the fluorescence shows the perfused vessels. The
tissue is stained and rephotographed to reveal the total capillary
network. Morphometric analysis is used to determine the parameters of
interest in the total and perfused capillary networks. The method has been
extensively validated in brain, muscle and omentum to show that the
technique does not alter the capillary network, that both the total and
perfused vessels are fully visualized and that there is little tissue
shrinkage. This technique will be applied to study the alterations in the
perfused capillary network of conscious Sprague Dawley rats. Prior surgery
will be done to catheterize a femoral artery and vein. These animals will
be used to study the effect of reductions in brain 02 supply. 02 supply
will be reduced by hypoxia, hypocapnia, anemia, carbon monoxide, hemorrhage
and stroke. This will provide new information on how the brain handles
reductions in 02 supply on a regional basis in terms of alterations in
diffusion distances. This new method allows study of the functional state
of the capillary bed in normal, stressful and disease conditions regionally
within an organ like brain and thus will allow a better understanding of
the control of the delivery of substances from blood to cell.
Effective start/end date7/1/836/30/86


  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)

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