Neurobiology course 20103.5.2010Group 7

Ivana MizikovaSalla KangasHenri Urpilainen

Introduction to BBB

• Originally found by Paul Ehrlich in 1885

• Complementary observations by Edwin Goldman 1913

• The localisation of the barrier was found: it separates the blood circulation from the brain tissue – the cellular basis was unclear

• BBB is located within endothelium in most vertebrates

Location of barrier sites in the CNS.Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrierNat. Rev. Neuro. 7: 41–53 doi:10.1038/nrn1824

Endothelial cells• BBB is formed by

endothelial cells, which form the capillars walls

• BBB endothelium differ from other endothelial structures

• BBB characteristics in endothelial cells is not pre-determined, but induced by environment

Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrierNat. Rev. Neuro. 7: 41–53 doi:10.1038/nrn1824

a) Fenestrated capillary in mouse eyec) Brain capillary in moused) Large vessel in mouse braine) Magnification from d showing the tight

junction

Junctions in endothelium

• Adherens junctions– Cadherins and integrins

• Tight junctions– Structure of tight junction in endothelial cells of

BBB is most complex among the entire vasculature of the body

– Impermeable barrier to fluid formed by closely associated membranes of two cells

Molecular composition of cell junctions

- Occludin (modulators)

- Claudin (barrier properties)

- Peripheral membrane proteins (cytoplasmic plaque, adaptor proteins) Abbott NJ et al. (2006) Astrocyte–endothelial

interactions at the blood–brain barrierNat. Rev. Neuro. 7: 41–53 doi:10.1038/nrn1824

Transporters in the BBB endothelium

• Delivery of vital molecules requires the presence of transporters, which are under the control of astrocytes– DOPA (metabolic BBB)– Glucose (main energy source of the brain)

• P-glycoprotein– Extrusion of nonpolar molecules out of

endothelial cells

Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrierNat. Rev. Neuro. 7: 41–53 doi:10.1038/nrn1824

The glio-vascular complex

• Involved in the regulation of blood flow and nutrient supply within the CNS

Regulation includes:1) Control of perfusion2) Maintenance of energy supply3) The protection of nervous

parenchyma

Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrierNat. Rev. Neuro. 7: 41–53 doi:10.1038/nrn1824

• Formed by astrocyte endfeet and pericytes together with endothelial cells

REMEMBER THIS!

• BBB is important barrier that protect the brain tissue from threats

• In the formation of BBB cooperate glial cells (astrocytes), pericytes, endothelial cells and extracellular components

• Specialized transport through BBB plays important role in brain tissue nutrition and homeostasis

• BBB is a dynamic structure under the close regulation of the brain microenvironment by astrocytes and pericytes

Thank you!