Pharmacology of the Blood-Brain Barrier

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Questions and Answers

Who is credited with the discovery of the blood-brain barrier?

Kristensson

Bentivoglio

Paul Ehrlich

Edwin Goldmann (correct)

What is the primary function of the blood-brain barrier?

To regulate blood pressure

To allow free passage of nutrients and oxygen to neurons

To facilitate immune system crosstalk with the nervous system

To selectively prevent pathogens, small hydrophilic molecules, and proteins from entering the CNS (correct)

What is the purpose of the receptor theory in pharmacology?

To describe the action of drugs on the immune system

To develop new strategies to overcome the blood-brain barrier

To postulate that the action of drugs are mediated via binding to cellular structures or receptors (correct)

To explain how the blood-brain barrier functions

What is an example of a specific disease where the blood-brain barrier is a target?

COVID-19 Signup and view all the answers

What is the result of the blood-brain barrier being diseased?

Disrupted immune-nervous system crosstalk Signup and view all the answers

What is the primary function of the blood-brain barrier in relation to nutrient and oxygen supply?

To facilitate the transport of nutrients and oxygen to neurons Signup and view all the answers

Who contributed to the understanding of the blood-brain barrier with their work on trypan blue injection?

Paul Ehrlich and Edwin Goldmann Signup and view all the answers

What is the blood-brain barrier in relation to the immune and nervous systems?

An interface for immune-nervous system crosstalk Signup and view all the answers

What is the main difference between peripheral capillaries and cerebral capillaries?

Cerebral capillaries are fenestrated while peripheral capillaries are not. Signup and view all the answers

What is the approximate length of vessels in a human brain?

600 km Signup and view all the answers

What is the function of pericytes in the neurovascular unit?

Influence on immune cell infiltration and blood flow regulation Signup and view all the answers

What is the main function of astrocytes in the neurovascular unit?

Water and ion homeostasis in the brain Signup and view all the answers

What is the main difference between the barrier properties of peripheral endothelial cells and brain endothelial cells?

Peripheral endothelial cells have a lower resistance than brain endothelial cells. Signup and view all the answers

What is the approximate resistance of brain capillaries?

1500-2000 Ω/cm2 Signup and view all the answers

What is the role of endothelial cells in the neurovascular unit?

Binding partner and regulator of immune cell trafficking Signup and view all the answers

What is the coverage of pericytes in the neurovascular unit?

Highest in brain vessels Signup and view all the answers

Study Notes

Blood-Brain Barrier (BBB)

The BBB is a selective barrier between blood and CNS compartments that:
- Prevents pathogens, small hydrophilic molecules, proteins, and leukocytes from entering the CNS
- Allows nutrient and oxygen supply to neurons
- Regulates blood pressure
- Forms an interface for immune- and nervous system crosstalk

Structure of the Blood-Brain Barrier (BBB)

The BBB consists of different barriers, including circumventricular organs and brain vasculature
Brain vasculature has:
- 600 km of vessels in the human brain
- Each neuron has its own capillary
- The largest barrier interface in the brain
Vessel composition differs between arterioles, capillaries, and venules
Cerebral capillaries:
- Are not fenestrated like peripheral capillaries
- Have a lower transcytotic rate than peripheral endothelial cells
- Have different barrier properties (~1500-2000 Ω/cm2 vs. ~30 Ω/cm2 in peripheral capillaries)
- Have an increased number of mitochondria
- Are covered with astrocytic endfeet
- Have the highest coverage of pericytes compared to peripheral vessels

Neurovascular Unit

The neurovascular unit consists of:
- Endothelial cells
- Pericytes/smooth muscle cells
- Astrocytes
- Neurons
Extended parts of the neurovascular unit include:
- Microglia
- Blood cells

Pericytes

Pericytes:
- Surround the endothelial cell layer
- Are embedded between the endothelial and parenchymal basement membrane
- Are important for the function and development of the BBB
- Influence several mechanisms in the brain (immune cell infiltration, blood flow regulation)
- Are a heterogeneous cell type dependent on vessel type

Astrocytes

Astrocytes:
- Have direct contact with vessels, neurons, synapses, and other glial cells
- Influence tightness and transport mechanisms across the BBB
- Are essential for water and ion homeostasis in the brain (special water and ion channels at their endfeet)
- Are highly reactive after disturbance

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Description

This quiz covers the basics of the blood-brain barrier, its structure, disease implications, and strategies to overcome the barrier. It also explores the BBB as a target for specific diseases, including COVID-19.