neuropeptide-y and Cerebrovascular-Disorders

Postmenopausal women represent the largest cohort of patients with heart failure with preserved ejection fraction, and vascular dementia represents the most common form of dementia in patients with heart failure with preserved ejection fraction. Therefore, we tested the hypotheses that the combination of cardiac pressure overload (aortic banding [AB]) and the loss of female sex hormones (ovariectomy [OVX]) impairs cerebrovascular control and spatial memory.. Female Yucatan miniswine were separated into 4 groups (n=7 per group): (1) control, (2) AB, (3) OVX, and (4) AB-OVX. Pigs underwent OVX and AB at 7 and 8 months of age, respectively. At 14 months, cerebral blood flow velocity and spatial memory (spatial hole-board task) were lower in the OVX groups (. Mechanistically, impaired cerebral blood flow control in experimental heart failure may be the result of heightened neuropeptide Y-induced vasoconstriction along with reduced vasodilation associated with decreased Ca

Topics: Animals; Aorta; Arterial Pressure; Behavior, Animal; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition; Cognition Disorders; Disease Models, Animal; Female; Gonadal Steroid Hormones; Heart Failure; Ligation; Neuropeptide Y; Nitric Oxide; Ovariectomy; Pia Mater; Potassium Channels, Calcium-Activated; Signal Transduction; Spatial Memory; Swine; Swine, Miniature; Time Factors; Vasoconstriction; Vasodilation

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.

Topics: Animals; Cerebral Cortex; Cerebrovascular Disorders; Diagnostic Imaging; Gene Expression; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Neurons; Neuropeptide Y; Neurovascular Coupling; Optogenetics; Organ Specificity; Oxygen; Photic Stimulation; Protein Binding; Receptors, Neuropeptide Y; Vasoconstriction; Vasoconstrictor Agents

We examined 5-hydroxytryptamine-like immunoreactive cerebrovascular nerve fibers in rats after experimental thromboembolic stroke. Although there were no visible 5-hydroxytryptamine-like immunoreactive nerve fibers in normal animals, we found many of these fibers near the clot emboli 30 min after the stroke, and the number of fibers increased slightly with time. In immunohistochemical double staining, these fibers corresponded to neuropeptide Y-like immunoreactive nerve fibers. And they were not observed in animals after superior cervical ganglionectomy. These findings suggest that the sympathetic nerves take up serotonin released from intraluminal aggregating platelets.

Topics: Animals; Cerebral Arteries; Cerebrovascular Disorders; Fluorescent Antibody Technique; Ganglionectomy; Immunohistochemistry; Intracranial Embolism and Thrombosis; Male; Nerve Fibers; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Serotonin; Sympathetic Nervous System