The blood-brain barrier refers to the highly
selective permeability of blood vessels within the central nervous system. The barrier controls, in a precise manner,
substances that can enter or leave the nervous tissue. It helps maintain the stable state, or homeostasis,
of brain tissue, amid the fluctuations of circulating substances in the blood, many
of which can act as neurotransmitters and could create chaos in neuronal activities
if allowed to diffuse freely into the brain. The barrier also protects the brain from blood-borne
pathogens and toxins. The blood-brain barrier is composed of several
cell types, including: - Endothelial cells that form the wall of
blood vessels; - Mural cells, namely pericytes, partially
covering the outside of endothelial cells; - And glial cells astrocytes, whose extended
processes, called end-feet, wrap around the vessels. The endothelial cells alone can fulfill the
functions of the blood-brain barrier, but their interactions with the adjacent cells
seem to be required for its formation, maintenance and regulation. The brain endothelial cells, unlike their
counterparts in other tissues, possess unique properties that allow them to tightly control
the passage of substances between the blood and brain. These properties can be classified into physical,
transport, and metabolic categories: - The brain endothelial cells are held together
by tight junctions, which serve as physical barriers, preventing movements of substances
through the space between cells. - They have very low rates of vesicle-mediated
transcellular transport. - They control the movement of ions and substances
with specific transporters, of which there are two major types: efflux transporters and
nutrient transporters: + Efflux transporters use cellular energy
to move substances against their concentration gradient. These transporters are usually located on
the blood side of endothelial cells. They transport lipophilic molecules, which
have passively diffused through the cell membrane, back to the blood. + Nutrient transporters, on the other hand,
facilitate the movement of nutrients, such as glucose and essential amino acids, into
the brain, down their concentration gradient. - The brain endothelial cells also contains
a number of enzymes that metabolize, and thus inactivate, certain neurotransmitters, drugs
and toxins, preventing them from entering the brain. An intact blood-brain barrier is critical
for normal brain functions. Neurological diseases such as encephalitis,
multiple sclerosis, brain traumas, Alzheimer's disease, epilepsy, strokes and tumors, can
breach the barrier, and this, in turn, contributes to disease pathology and further progression. To note, however, that not all areas of the
brain have the blood-brain barrier. For example, some brain structures are involved
in hormonal control and require better access to systemic blood, so they can detect changes
in circulating signals and respond accordingly. These non-barrier areas are located around
the midline of the ventricular system, and are known as circumventricular organs. Some of their bordering regions have a leaky
barrier. The blood-brain barrier also has its downside. While it protects the brain from unwanted
drugs and toxins, it also prevents therapeutic drugs from entering the central nervous system
to treat diseases. Several strategies are developed to overcome
this obstacle, including: - delivering the drug directly into the cerebrospinal
fluid; - use of vasoactive compounds;
- designing drugs with higher lipid solubility; - hacking the endogenous transport system
to carry the drug, - and blocking the efflux transporter that
pumps the drug back to the bloodstream.
