PhD Project - (Bicentenary) Vascular Consequences of Menopause in the Female Brain at The University of Manchester, listed on FindAPhD.com

Growing evidence suggests that reduced cerebral blood flow contributes to cognitive decline in ageing and dementia. Attwell and colleagues discuss the underlying mechanisms and functional consequences...

SignificanceBehavior regulates dural and cerebral vessels, with spontaneous locomotion inducing dural vessel constriction and increasing stimulus-evoked cerebral hemodynamic responses. It is vital to investigate the function of different vascular network components, surrounding and within the brain, to better understand the role of the neurovascular unit in health and neurodegeneration.AimWe characterized locomotion-induced hemodynamic responses across vascular compartments of the whisker barrel cortex: artery, vein, parenchyma, draining, and meningeal vein.ApproachUsing 2D-OIS, hemodynamic responses during locomotion were recorded in 9- to 12-month-old awake mice: wild-type, Alzheimer’s disease (AD), atherosclerosis, or mixed (atherosclerosis/AD) models. Within the somatosensory cortex, responses were taken from pial vessels inside the whisker barrel region [(WBR): “whisker artery” and “whisker vein”], a large vein from the sagittal sinus adjacent to the WBR (draining vein), and meningeal vessels from the dura mater (which do not penetrate cortical tissue).ResultsWe demonstrate that locomotion evokes an initial decrease in total hemoglobin (HbT) within the draining vein before the increase in HbT within WBR vessels. The locomotion event size influences the magnitude of the HbT increase in the pial vessels of the WBR but not of the early HbT decrease within the draining veins. Following locomotion onset, an early HbT decrease was also observed in the overlying meningeal vessels, which unlike within the cortex did not go on to exceed baseline HbT levels during the remainder of the locomotion response. We show that locomotion-induced hemodynamic responses are altered in disease in the draining vein and whisker artery, suggesting this could be an important neurodegeneration biomarker.ConclusionsThis initial reduction in HbT within the draining and meningeal veins potentially serves as a “space-saving” mechanism, allowing for large increases in cortical HbT associated with locomotion. Given this mechanism is impacted by disease, it may provide an important target for vascular-based therapeutic interventions.

Discover how Rahul Sidhu is exploring the link between heart disease and Alzheimer’s, uncovering how vascular health impacts neurodegeneration.