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Structural abnormalities in brain microvasculature are commonly associated with Alzheimer's Disease and other
dementias. However, the extent to which structural microvascular abnormalities cause functional impairments in brain
circulation and thereby to cognitive impairment is unclear. Non-invasive, near-infrared spectroscopy (NIRS) methods
can be used to determine the absolute hemoglobin concentration and saturation in brain tissue, from which additional
parameters such as cerebral blood volume (a theoretical correlate of brain microvascular density) can be derived.
Validating such NIRS parameters in animal models, and understanding their relationship to cognitive function is an
important step in the ultimate application of these methods to humans. To this end we applied a non-invasive multidistance
NIRS method to determine the absolute concentration and saturation of cerebral hemoglobin in rat, by
separately measuring absorption and reduced scattering coefficients without relying on pre- or post-correction factors.
We applied this method to study brain circulation in folate deficient rats, which express brain microvascular pathology1
and which we have shown to develop cognitive impairment.2 We found absolute brain hemoglobin concentration
([HbT]) and oxygen saturation (StO2) to be significantly lower in folate deficient rats (n=6) with respect to control rats
(n=5) (for [HbT]: 73±10 μM vs. 95±14 μM; for StO2: 55%±7% vs. 66% ±4%), implicating microvascular pathology and
diminished oxygen delivery as a mechanism of cognitive impairment. More generally, our study highlights how noninvasive,
absolute NIRS measurements can provide unique insight into the pathophysiology of Vascular Cognitive
Impairment. Applying this method to this and other rat models of cognitive impairment will help to validate
physiologically meaningful NIRS parameters for the ultimate goal of studying cerebral microvascular disease and
cognitive decline in humans.
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