Sepsis is a life-threatening condition, the incidence of which is significantly increased
in elderly patients. One of the long-lasting effects of sepsis is cognitive impairment
defined as a new deficit or exacerbation of preexisting deficits in global cognition
or executive function. Normal brain function is dependent on moment-to-moment adjustment
of cerebral blood flow to match the increased demands of active brain regions. This
homeostatic mechanism, termed neurovascular coupling (NVC, also known as functional
hyperemia), is critically dependent on the production of vasodilator NO by microvascular
endothelial cells in response to mediators released from activated astrocytes. The
goal of this study was to test the hypothesis that sepsis in aging leads to impairment
of NVC responses early after treatment and that this neurovascular dysfunction associates
with impairments in cognitive performance and vascular endothelial dysfunction. To
test this hypothesis, we used a commonly studied bacterial pathogen, Listeria monocytogenes,
to induce sepsis in experimental animals (males, 24 months of age) and subjected experimental
animals to a standard clinical protocol of 3 doses of ampicillin i.p. and 14 days
of amoxicillin added to the drinking water. NVC responses, endothelial function and
cognitive performance were measured in septic and age-matched control groups within
14 days after the final antibiotic treatment. Our data demonstrate that sepsis in
aging significantly impairs NVC responses measured in somatosensory cortex during
whisker stimulation, significantly impairs endothelial function in isolated and pressure
cannulated aorta rings in response to acetylcholine stimulation. No significant impairment
of cognitive function in post-sepsis aged animals has been observed when measured
using the PhenoTyper homecage based system. Our findings suggest that sepsis-associated
endothelial dysfunction and impairment of NVC responses may contribute to long-term
cognitive deficits in older sepsis survivors.
