CEREBRAL ISCHEMIA AND FREE OXYGEN RADICALS

Project: Research project

Description

Although the pathophysiologic response of the brain to a reduced
oxygen availability has been studied for many years the exact
mechanism by which cerebral damage is incurred is not known. It
is also unclear whether the mechanism of damage is the same for
ischemia (a reduction in cerebral blood flow) and hypoxia (a
reduction in blood oxygen content). The overall goals of this
project are to clarify the role of oxygen derived free radical
mechanisms in the pathophysiology of global cerebral ischemia
and hypoxia and to determine if the apparent ability of newborn
animals to tolerate reduced cerebral oxygen availability is related
to a free radical mechanism. We hypothesize that increasing the
duration of an ischemic insult is associated with decreased
recovery of post ischemic cerebral blood flow and oxygen
consumption, decreased post ischemic recovery of neurologic
function and increased post ischemic production of oxygen derived
free radicals, but that these changes will be less marked in
newborns. Likewise, we hypothesize that there will be an
increased release of oxygen derived free radicals during
reoxygenation after pure hypoxia. Ischemia will be induced by
cross clamping the ascending aorta after occlusion of the vena
cavae. In both newborn and older animals ischemia will be
maintained for variable times to determine whether changing the
interval of ischemia or the administration of oxygen derived free
radical scavengers (e.g. superoxide dismutase) has an effect on
post ischemic sequela. The variables that will be measured
include cerebral blood flow (radiolabelled microsphere technique),
cerebral oxygen consumption (Fick principle), cerebral function
(evoked potentials) and production of oxygen derived free radicals
(nitroblue-tetrazolium technique). Cerebral hypoxia will be
produced by lowering the inspired oxygen content while
maintaining arterial PCO2 and pH normal. In this group of
animals hypoxia will be maintained at one of two levels (5% or
10% O2) for ten minutes and the rate of free radical production
will be determined during reoxygenation. From our data we will
be able to determine whether oxygen derived free radical
mechanisms are associated with cerebral ischemia or hypoxia.
StatusFinished
Effective start/end date8/1/877/31/92

Funding

  • National Institutes of Health
  • National Institutes of Health: $79,180.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Brain Ischemia
Free Radicals
Reactive Oxygen Species
Oxygen
Cerebrovascular Circulation
Brain Hypoxia
Ischemia
Newborn Animals
Brain Hypoxia-Ischemia
Nitroblue Tetrazolium
Microspheres
Evoked Potentials
Constriction
Oxygen Consumption
Superoxide Dismutase
Aorta
Brain
Hypoxia

ASJC

  • Medicine(all)
  • Neuroscience(all)