What is the blood-brain barrier (not)?

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• The historical concept of the blood-brain barrier (BBB) is based on early observations of molecular restriction by brain capillaries.
• The term 'Bluthirnschranke' (blood-brain barrier, BBB) has evolved, but its application to leukocyte recruitment is imprecise.
• Early work by Ehrlich, Lewandowski, and Goldmann established the BBB's role in solute transport.

Purpose of the Study:

• To redefine the blood-brain barrier (BBB) as a capillary barrier specifically for solutes.
• To clarify the precise mechanisms and steps involved in leukocyte recruitment into the brain.
• To propose a novel role for perivascular antigen recognition and ectoenzymes in leukocyte transmigration.

Main Methods:

• Re-evaluation of historical experimental data on molecular transport across brain capillaries.
• Analysis of the distinct phases of leukocyte migration into the central nervous system.
• Investigation of molecular mediators, including matrix metalloproteinases (MMPs), in leukocyte extravasation.

Main Results:

• The BBB is redefined as a barrier primarily controlling the passage of solutes across brain capillaries.
• Leukocyte recruitment into the brain is a two-step process: crossing postcapillary venules and then the glia limitans.
• The second step of leukocyte entry into the neuropil may involve antigen recognition and MMP induction.

Conclusions:

• The BBB's primary function is solute restriction, not the inhibition of leukocyte trafficking.
• Leukocyte recruitment into the brain involves distinct vascular and parenchymal barriers.
• Perivascular antigen recognition and MMPs are proposed as key regulators of leukocyte entry into the neuropil.