The blood-brain barrier: barrier or customs border?
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1 The blood-brain barrier: barrier or customs border? Jerome Badaut, Phd Brain Molecular Imaging group
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4 Badaut et al Neuro (green) vascular (red) unit (NVU) (Obenaus, Coats, Krucker) (brain s vascular network) Vasculature: Backbone for neurons
5 The Blood-Brain Barrier or The Blood-Brain Border (BBB)? 1) Introduction: - History - Neurovascular Unit and BBB - Role in transport -Cell trafficking and immune privilege organ 2) Is BBB identical in brain regions? - circumventricular organs - brain regions 3) BBB changes in brain disorders - After brain injuries - In chronic brain disorders
6 The blood-brain barrier: historical introduction Erlich, 1885 and Goldman 1913
7 The blood-brain barrier: where are located the barriers? 1) Brain endothelium 2) Choroid plexus epithelium 3) Choroid plexus epithelium For review Abbott J. Nature Neurosci Rev, 2006
8 The blood-brain barrier: BBB in the neurovascular unit 1) Endothelial cell 2) Pericyte 3) Astrocyte 4) Microglia 5) Immune cells 6) Neurons For review Abbott J. Nature Neurosci Rev, 2006
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10 The blood-brain barrier: Physical barrier with a tight junctions For review Abbott J. Neurobiology of Disease, 2010
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12 The blood-brain barrier: Custom border for blood solutes For review Abbott J. Neurobiology of Disease, 2010
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14 The blood-brain barrier: Custom border for blood cells NVU: Architecture of a medieval castle: with a moat (blue, CSF) and double wall Medieval castle Pirou in Normandy: with a moat For review: Muldoon L.L. et al., JCBFM 2013 Abbott J. Neurobiology of Disease, 2010
15 The blood-brain barrier: Custom border for blood cells NVU: Architecture of a medieval castle: with a moat (blue, CSF) and double wall For review: M.A. Lopes Pinheiro et al. BBA 2016
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17 The blood-brain border: The opened window on the blood stream Subfornical organ Organum vasculosum of the lamina terminalis E. E. Benarroch Neurology 2011
18 The blood-brain border: Are transporters/ carriers similarly distributed? J.N. Abbott et al. Neuorbiol of disease 2010
19 The blood-brain border: Difference in Glucose transporter (GLUT1) Cortex Cortex GLUT-1 PVN EBA PVN Badaut et al. J of Neuroendocrinology 2000
20 The blood-brain border: Is BBB identical in the same vascular tree? Iadecolla Neuron 96, Sept 2017
21 The blood-brain border: Heterogeneity in the brain vasculature PgP (purple) not expressed in the arterioles (yellow) but in veins Saubaméaet al., JCBFM 2012
22 The blood-brain border: Heterogeneity in the brain vasculature Endothelial Brain Antigen (EBA, purple) shows heterogeneity in capillary and veins Saubaméaet al., JCBFM 2012
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24 The Blood-Brain Border: DISRUPTION!!! Traumatic Brain Injury: BBB disruption, opening, dysfunction in pathology Pop & Badaut, (2011) TSR
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26 The Blood-Brain Border: Changes in tight junction properties after stroke? Haley MJ and Lawrence CB, JCBFM 2016
27 The blood-brain border: Increase of trancystosis after stroke BBB Hyper-permeability after stroke: Increase of Caveolae/ Trancytosis Knowland et al., Neuron 2014
28 The blood-brain barrier: Does BBB recover after brain injury? Pop & Badaut, (2011) TSR Pop et al., JCBFM 2013
29 Aβ traffic through the Blood-Brain Barrier (blood) Aβ clearance Pgp (Tight Junctions Claudin 5.) (endothelial cells) (brain) LRP1 Aβ P-glycoprotein (P-gp) ATP binding-cassette multidrug resistance protein Limits entry of exogenous molecules and Aβ on luminal side. Low-density lipoprotein receptor-related protein-1 (LRP1) Endocytic receptor for cholesterol transport and metabolism. Clears Aβ from abluminal side (efflux transporter) Modified from Andras et al., Mol Cell Neurosci. 201
30 Decrease of P-glycoprotein 2-months after jtbi SHAM PgP GFAP jtbi PgP GFAP Pop et al., JCBFM 2013
31 Vascular and diffuse Aβ at 2 months after jtbi Aβ DAPI Aβ DAPI Pop et al. JCBFM 2013
32 3 Months 36 Months P-glycoprotein
33 The Blood-Brain Barrier or The Blood-Brain Border (BBB)? TAKE HOME MESSAGE 1) Is BBB identical in brain regions? - NO - Little is known between BBB phenotype and brain regions - How does BBB phenotype change in life span - How does BBB phenotype evolve under certain physiological conditions? 2) BBB disruption, opening - After brain injuries not only physical opening - Blood-brain barrierosis after acute injury - Phenotypic transformation
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