neurobiology course 2010 3.5.2010 group 7 ivana mizikova salla kangas henri urpilainen
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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!