Voluntary locomotion induces an early and remote hemodynamic decrease in the large cerebral veins

Area of Science:

• Neuroscience
• Vascular Biology
• Neurodegenerative Diseases

Background:

• Behavioral activity significantly influences cerebral blood flow dynamics.
• Understanding the neurovascular unit's role in health and disease, particularly neurodegeneration, is crucial.
• Investigating vascular network components within and around the brain is vital.

Purpose of the Study:

• To characterize locomotion-induced hemodynamic responses across different vascular compartments in the mouse whisker barrel cortex.
• To compare these responses in wild-type mice versus models of Alzheimer's disease (AD) and atherosclerosis.

Main Methods:

• Utilized 2D-OIS to record hemodynamic responses during locomotion in awake mice (9-12 months old).
• Analyzed responses in pial arteries and veins within the whisker barrel region (WBR), draining veins, and meningeal vessels.
• Included wild-type, AD, atherosclerosis, and mixed (atherosclerosis/AD) mouse models.

Main Results:

• Locomotion initially decreased total hemoglobin (HbT) in draining veins before increasing HbT in WBR vessels.
• Locomotion event size affected WBR pial vessel HbT increase but not the early draining vein HbT decrease.
• Meningeal vessels showed an early HbT decrease post-locomotion, not exceeding baseline.
• Locomotion-induced hemodynamic responses were altered in disease models within the draining vein and whisker artery.

Conclusions:

• An initial HbT reduction in draining and meningeal veins may facilitate large cortical HbT increases during locomotion.
• This "space-saving" mechanism is impacted by neurodegenerative diseases.
• Altered vascular responses in disease suggest potential biomarkers and targets for vascular-based therapies.