Dysfunction of Mouse Cerebral Arteries during Early Aging

Abstract

Aging leads to a gradual decline in the fidelity of cerebral blood flow (CBF) responses to neuronal activation, resulting in an increased risk for stroke and dementia. However, it is currently unknown when age-related cerebrovascular dysfunction starts or which vascular components and functions are first affected. The aim of this study was to examine the function of microcirculation throughout aging in mice. Microcirculation was challenged by inhalation of 5% and 10% CO 2 or by forepaw stimulation in 6-week, 8-month, and 12-month-old FVB/N mice. The resulting dilation of pial vessels and increase in CBF was measured by intravital fluorescence microscopy and laser Doppler fluxmetry, respectively. Neurovascular coupling and astrocytic endfoot Ca 2+ were measured in acute brain slices from 18-month-old mice. We did not reveal any changes in CBF after CO 2 reactivity up to an age of 12 months. However, direct visualization of pial vessels by in vivo microscopy showed a significant, age-dependent loss of CO 2 reactivity starting at 8 months of age. At the same age neurovascular coupling was also significantly affected. These results suggest that aging does not affect cerebral vessel function simultaneously, but starts in pial microvessels months before global changes in CBF are detectable.

Acute changes in neurovascular reactivity after subarachnoid hemorrhagein vivo

“…At the same time, a continuous intra-arterial infusion of ketamine (30 mg/ kg/h, Inresa, Freiburg, Germany) was initiated. 18 …”

“…Arteriolar diameters were quantified with a calibrated image analysis software (Zen, Zeiss, Oberkochen, Germany) and expressed in percentage of baseline as previously described. 18 Vessel diameter during forepaw-evoked NVC For evaluation of changes in vessel diameter after forepaw stimulation, the same protocol as for assessment of CBF was used. Briefly, the region yielding the most pronounced CBF response was stimulated with one stimulation cycle, contained 96 stimulations and lasted for 16 s (6 Hz).…”

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

“…There is growing evidence that functional impairment of the neurovascular unit develops early during aging before manifestation of other pathologies (Balbi et al 2015), and that it importantly contributes to age-related impairment of brain function (Tarantini et al 2016;Toth et al 2017). The energetic demand of active neurons is high and their proper function depends on constant, tightly controlled delivery of oxygen and nutrients via the microcirculatory network.…”

Arterial hypertension impact on cerebral blood flow in patients with Alzheimer’s disease

“…The ability of the endothelium to relax the smooth muscle cells of the arterial wall is then impaired, limiting the possibilities of arterial vasomotoricity in physiological or pathological conditions. 32,33 In 2007, Stoquart-El Sankari confirmed that cerebral blood flow decreases with age regardless of the study technique 30,31 . She observed a decrease in the cerebral blood flow in the elderly with preserved compliance.…”

“…Because the average age of our Alzheimer's patients were similar for both groups with and without hypertension, the groups were easily comparable. Age is a major risk factor for AD, 28 hypertension 29 and cerebrovascular changes develop with age 30,31 , influencing the results of blood flow. With age, arterial changes appear: intimal thickening, the destruction of endothelial cells, and smooth muscle cells losing their contractile phenotype to a secretory phenotype.…”