Cellular and Molecular Neuroscience

The Blood Brain Barrier (BBB)

Guardian against toxins

Selective gatekeeper

Prevents harmful substances, pathogens and large molecules from entering the brain

Allows the passage of essential nutrients, oxygen, and hormones while restricting others

BBB

Term used to describe the unique properties of the microvasculature of the CNS

Formed by brain capillary endothelial cells (BCECs) lining neurovasculature

BCECs surrounded by pericytes and astrocytic endfeet

Together cells of BBB make up neurovascular unity (NVU)

Unique properties of BCECs restrict access of blood borne substances

BCECs tightly joined together restricting entry of substances

Properties allow BCECs to tightly regulate movement of molecules, ions, and cells between blood and CNS

Carrier Mediated Transcytosis

Molecules like glucose, are carried across the BCECs via specific solute carriers/carrier proteins

Solutes (e.g. glucose) will bind to protein transporter

This will lead to conformational change

Carrier will then transport substance to other side of membrane

Usually from high to low concentration

If against concentration gradient, requires ATP to provide the energy to facilitate the process

Absorptive Mediated Transcytosis

Positively charged molecules like L-DOPA enter the brain via absorptive mediated transcytosis

Positively charged substance in bloodstream associate with negatively charged membrane surface

This induces membrane invagination and vesicle formation

Substance-containing vesicle will enter intracellular space

Move to other (abluminal) side and release contents

Receptor Mediated Transcytosis

Macromolecules (e.g. insulin, transferrin) enter via receptor binding which triggers an endocytotic event and subsequent transportation across the BBB

Ligand binds to receptor

Initiates invagination of membrane and endocytosis process

In the cell the vesicle can be:

recycled back out into capillary

Fuse with membrane on other side allowing for content release

Fuse with lysosome and be degraded

BBB is major obstacle preventing life-saving treatments from reaching the brain

Treatments for various CNS diseases limited because of BBB permeability

treatments may exist but just can't pass BBB due to their characteristics

Astrocytes

Now BBB restricts access to many things but will act as a gatekeeper

Great structure to have given the sensitivity of brain tissue

There are different ways substances cross the BBB

Notice though that the BBB/neurovascular unit (NVU) has this thing called astrocyte endfeet

These are part of another cell in the brain called the astrocyte (another type of glial cell)

Astrocytes provide nutritional support to neurons. One astrocyte can make contact with thousands of neurons. Provides nutritional support to neurons, but not the only thing.