Blood Brain Barrier - Anatomy & Physiology

Structure and Function

Endothelial cells are the structural basis of the blood brain barrier and are joined by tight cellular junctions. These junctions are impermeable to proteins and also restrict the passage of non-lipid soluble molecules. Within the BBB, most molecules use carrier systems. The properties of the BBB are induced and probably maintained by molecules secreted by astrocytes. The BBB prevents circulating antibodies reaching the central nervous system (CNS) and thus is a component of the immunological privilege manifest by the CNS. The BBB is not considered to affect the movement of inflammatory cells into the CNS; activated lymphocytes can enter the normal CNS.

Inflammatory responses in the CNS are different to elsewhere in the body. Injections of lipopolysaccaride, which would result in massive influx of granulocytes (polymorphonuclear leukocytes (PML)) in peripheral tissue result in no influx into the brain substance, however influx into CSF does occur.

Defects of the Blood Brain Barrier

VASOGENIC OEDEMA

This BBB defect causes the BBB to break down in many pathological situations, e.g around brain tumours and when there is inflammation in the CNS. When this happens protein rich fluid spreads through the extracellular space of the brain, and is termed vasogenic oedema and since there are no lymphatic channels in the CNS, the excess fluid flows down pressure gradients, making its way to white matter and eventually to the ventricles. The presence of protein rich fluid causes astrocytes and microglial cells to react, causing astrocyte hypertrophy, swelling and upregulate many molecules. Microglia express MHC-2 molecules and take up plasma proteins. The presence of extra fluid in the extracellular space results in an increase in brain volume.

CYTOTOXIC OEDEMA

It is important to distinguish the brain swelling which results from the presence of plasma in the extracellular space from the brain swelling that occurs as a consequence of cell swelling. Accumulation of fluid within cells, cytotoxic oedema is a common manifestation of many neurotoxic situations. It usually affects specific cells, or even parts of cells with the location being a reflection of the metabolic process being blocked by the neurotoxin:

• Hexochlorophene and tri-ethyl tin cause fluid to accumulate in myelin sheaths
• Cyanide caused swelling of axons
• Interfering with energy generation causes swelling of astrocytes.

The distinction between cytotoxic and vasogenic oedema is important clinically when one is trying to decrease brain volume using hyperosmolar agents since one can only decrease brain volume with these agents when the BBB is intact.