Neurovascular Coupling: Flashcards
Describe the Anatomical Features of the Blood Supply to the Brain
Major Arteries:
Internal Carotid Arteries (ICA): Supply the anterior 2/3 of the cerebrum.
Vertebral Arteries: Form the basilar artery, which supplies the posterior 1/3 of the brain.
Circle of Willis: An anastomotic ring connecting the anterior and posterior circulations.
Pial Vessels:
Surface arteries that give off penetrating branches, which dive into the brain cortex.
Virchow-Robin Space:
Perivascular spaces surrounding penetrating arteries, allowing exchange of solutes between cerebrospinal fluid (CSF) and interstitial fluid.
Regional Heterogeneity in Capillary Density:
High capillary density in regions with elevated metabolic demand (e.g., gray matter > white matter).
Describe neurone-to-astrocyte signalling:
Active neurones release glutamate, a major excitatory neurotransmitter
Glutamate binds to metabotropic glutamate receptors (mGluRs) on astrocytes, these are G-protein coupled receptors
This activates intracellular signalling pathways, leading to an increase in astrocytic intracellular calcium (Ca²⁺)
Increase in astrocytic Ca²⁺ can spread to neighbouring astrocytes via gap junctions, amplifying the response across a network
Describe astrocyte-to-vessel signalling by potassium:
Neuronal activity increases extracellular K⁺ levels, which astrocytes buffer to maintain ionic balance
Astrocytes release K⁺ near vascular smooth muscle cells (VSMCs) via Kir4.1 potassium channels
Elevated extracellular K⁺ hyperpolarizes VSMCs, causing relaxation and vasodilation
Describe astrocyte-to-vessel signalling by Arachidonic Acid Metabolites:
Astrocytes metabolise arachidonic acid to produce vasoactive compounds
Ca2+ dependent phospholipase A2 activation causes accumulation of arachidonic acid
High oxygen - production of prostaglandins (e.g., PGE2) leads to vasodilation
Low oxygen - formation of 20-HETE promotes vasoconstriction
Prostaglandin E2 (PGE2) released by astrocytes binds to EP receptors on endothelial cells or VSMCs, inducing relaxation
Describe Vasoactive Neurotransmitters and Interneurons:
Inhibitory interneurons release NO, contributing to vasodilation in response to neural activity
Vasoactive Intestinal Peptide (VIP): Enhances vasodilation through cAMP signalling
Substance P and Neurokinin A: Released by certain interneurons, these neuropeptides influence vascular tone
Describe cerebrovascular relationships
The interaction between neurones, astrocytes, and endothelial cells ensures tight regulation of cerebral blood flow (CBF) in response to neural activity
Capillary-Level Regulation - Pericytes, located on capillaries, respond to signals from astrocytes and endothelial cells to modulate capillary diameter and regulate blood flow
Describe blood flow regulation by metabolic signals and endothelial derived factors:
Metabolic signals:
- Increased neural activity raises extracellular CO₂ and lowers O₂, causing acidosis
- CO₂ readily diffuses into vascular endothelial cells, where it forms carbonic acid and dissociates into H⁺, promoting vasodilation via endothelial mechanisms
Endothelial derived factors:
- Endothelial cells also release vasoactive substances like NO and endothelin, modulating local blood flow
Describe the functional imaging implications:
Blood-Oxygen-Level Dependent (BOLD) fMRI:
NVC underpins the BOLD signal, reflecting changes in the ratio of oxy- to deoxyhemoglobin.
Increased neuronal activity causes localized vasodilation, increasing CBF and reducing deoxyhemoglobin levels, which enhances the fMRI signal.
Regional Variability:
Differences in capillary density and metabolic demand (e.g., gray matter vs. white matter) influence the magnitude of the BOLD signa
