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 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 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 Regulation includes: 1)Control of perfusion 2)Maintenance of energy supply 3)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 Formed by astrocyte endfeet and pericytes together with endothelial cells

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!