Neurobiology course 2010 3.5.2010 Group 7

1. Neurobiology course 2010 3.5.2010 Group 7 Ivana Mizikova Salla Kangas Henri Urpilainen

2. 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

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

4. Endothelial cells • BBB is formedbyendothelialcells, whichform the capillarswalls • BBB endotheliumdifferfromotherendothelialstructures • BBB characteristics in endothelialcells is notpre-determined, butinducedbyenvironment Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrier Nat. Rev. Neuro.7: 41–53 doi:10.1038/nrn1824

5. a) Fenestrated capillary in mouse eye c) Brain capillary in mouse d) Large vessel in mouse brain e) Magnification from d showing the tight junction

6. 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

7. 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 barrier Nat. Rev. Neuro.7: 41–53 doi:10.1038/nrn1824

8. 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

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

10. The glio-vascular complex • Involved in the regulation of blood flow and nutrient supply within the CNS • Formed by astrocyte endfeet and pericytes together with endothelial cells • Regulation includes: • Control of perfusion • Maintenance of energy supply • The protection of nervous parenchyma Abbott NJ et al. (2006) Astrocyte–endothelial interactions at the blood–brain barrier Nat. Rev. Neuro.7: 41–53 doi:10.1038/nrn1824

11. 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

12. Thank you!