Blood-Brain Barrier

These flashcards cover key concepts and details from the lecture on the Blood-Brain Barrier, providing a focused study tool for exam preparation.

What was the first experiment conducted by Paul Ehrlich in the 1800s?

He injected blue dye into the blood of animals and found that all organs turned blue except the brain.

What conclusion was drawn from Edwin Goldman's second experiment?

There is a protective barrier between the blood and the brain, known as the Blood-Brain Barrier.

When was the physical location of the blood-brain barrier confirmed?

In the 1960s.

What technology was used to see the blood-brain barrier during its confirmation?

Powerful electron microscopes and special tracers like horseradish peroxidase.

What forms the Circle of Willis?

The connection of two carotid arteries and two vertebral arteries at the base of the brain.

What type of arteries branch out from the Circle of Willis?

Large pial arteries.

What structure covers the outer surface of the brain's capillaries?

End-feet of astrocytes.

How many key features do the brain's blood vessels have?

Two: complexity and density.

What makes the blood-brain barrier located in brain capillaries?

A single layer of endothelial cells.

What connections do endothelial cells at capillary walls form?

Tight junctions and adherens junctions.

What is the Neurovascular Unit?

A team of cells that includes neurons, astrocytes, microglia, oligodendrocytes, and pericytes.

What is the role of astrocytes in the neurovascular unit?

They provide energy and nutrient support to neurons, maintain ion and water homeostasis, terminate synaptic activity, help maintain the BBB, and regulate breathing.

What does the perivascular sheath refer to?

The layer of astrocyte end-feet surrounding the brain's capillaries.

What is the glia limitans?

A layer of end-feet that forms a barrier just below the pia mater.

What is paracellular movement?

The movement of molecules between cells.

What is transcellular movement?

The movement of molecules through an endothelial cell.

How many types of transcellular movement are there?

Two: passive diffusion and transporters.

What are tight junctions?

The most important component that creates the blood-brain barrier by blocking the paracellular pathway.

What is the 'Gate' function of tight junctions?

They block the paracellular pathway, preventing leakage between cells.

What is Transendothelial Electrical Resistance (TEER)?

A measure of how tightly the endothelial cells are joined together, indicating the barrier's strength.

Why do brain capillaries have a very high TEER value?

It confirms the barrier's strength and restrictiveness.

Which junctions are found in the capillary wall?

Adherens junctions and tight junctions.

What type of molecules can typically pass through the blood-brain barrier?

Fat-soluble molecules can cross more easily.

What are the two main types of transport mechanisms mentioned?

Receptor-mediated transcytosis and absorptive transcytosis.

What is receptor-mediated transcytosis?

A selective process where a specific molecule binds to its receptor to facilitate transport.

What is the role of metabolic enzymes in the blood-brain barrier?

To break down molecules before they enter the brain.

What is the function of the Blood-Brain Barrier (BBB)?

To control molecule influx into the brain and supply essential nutrients.

What diseases require drugs to cross the BBB?

Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and others.

What is Amyloid-beta associated with in Alzheimer's disease?

Its buildup in the brain due to impaired clearance across the blood-brain barrier.

What is the Blood-CSF barrier?

The barrier located between the blood and cerebrospinal fluid (CSF).

Where are the choroid plexuses located?

In the ventricles of the brain.

What type of cells forms the lining of blood-brain barrier capillaries?

Endothelial cells.

What are P-glycoprotein's main functions?

It acts as an efflux transporter at the blood-brain barrier.

What kind of molecules do ABC transporters typically pump?

Lipophilic planar molecules.

How do glucose transporters function in the BBB?

They facilitate glucose's entry into the brain despite its water solubility.

What happens to morphine's efficacy at the BBB?

It has low lipophilicity and cannot easily cross the BBB.

What condition does the blood-brain barrier's 'tightness' facilitate?

Restricts ions and maintains stable ionic composition.

What is a significant obstacle for drugs trying to treat brain disorders?

The function of efflux transporters that remove drugs from the brain.

What is one of the key definitions for transporters in the brain?

Proteins that help specific substances cross cell membranes.

How do transporters differ based on molecule class?

Different transporters exist for neutral, acidic, and basic amino acids.

How does the reduced number of vesicles in brain capillaries affect permeability?

It makes the capillary barrier much tighter.

What do adherens junctions in brain capillaries do?

Act like 'spot welds' to hold cells together.

What is a key feature of the blood-brain barrier's structure?

Continuous strands of tight junctions.

What happens when tight junction integrity is compromised in the BBB?

It could lead to increased permeability and potential brain damage.

How does the blood-brain barrier protect the brain?

By restricting ionic fluctuations and providing stable interstitial fluid.

What is a potential role of astrocytes in neural activity regulation?

They help terminate synaptic communication.

Why is the regulation of potassium ions important in the brain?

They help maintain the electrochemical balance necessary for neuronal signaling.

What major structural protein is associated with tight junctions?

Claudins.

What ensures that neurons remain within 1-2 cells of a capillary?

The dense network of capillaries in the brain.

What type of movement occurs through the paracellular pathway?

Movement between endothelial cells.

What is the role of LRP1 in Alzheimer's disease?

It is involved in the clearance of Amyloid-beta across the blood-brain barrier.

Which barrier is specifically responsible for separating blood from cerebrospinal fluid?

Blood-CSF Barrier.

What happens during receptor-mediated transcytosis?

Specific molecules trigger vesicle formation for transport across the barrier.

What is the relationship between alcohol and the blood-brain barrier?

Alcohol can easily cross the barrier due to its lipophilicity.

How does the density of transporters in the BBB affect brain nutrition?

It provides efficient transport of essential nutrients like glucose.

In the context of astrocyte functions, what does 'ending signals' refer to?

Astrocytes help terminate neurotransmitter activity at synapses.

How can drug developers optimize their molecules for BBB permeability?

By increasing lipophilicity to enhance crossing efficiency.

What structure illustrates the intricate network of brain capillaries?

The injected brain with India ink.

What could happen if the blood-brain barrier is compromised?

It may lead to neuroinflammation and damage.