BBB 1.pptx

Blood brain barrier

1. Blood-brain barrier

2. Blood-brain barrier BBB forms physical resistance to passage of lipophobic substances from cerebral capillaries into brain. It protect CNS from major fluctuations of blood,provide stable neuronal transmission Protects from endogenous and exogenous toxins Helps in holding neurotranmitters which is specially required. BBB components include : E ndothelial cell layer and basement membrane - adjoined by tight cell to cell junction proteins ,no interendothelial gaps seen Pericytes Astroglial foot process - forms an additional continuous stratum that separates blood vessels from brain tissues

3. Circumventricular organs BBB is weak allows substance to pass through,for hormonal control they need systemic circulation Leaky region are isolated from rest of brain by specialized ependymal cells called tanycytes Examples Pineal body Posterior pituitary Area postrema

4. Agents impairs BBB Bradykinin,histamines,serotonin ATP,ADP,AMP MIP1,MIP2 AGENTS TIGHTS BBB Steroids Intracellular cAMP

5. Endothelial cell Lines brain capillaries Tight intercellular junction without fenestration. Greater number and volumes of mitochondria content seen in p-glycoprotein which is multidrug non- specificactive transporters Selective molecular permeability of BBB No pinocytosis or rare No sinusoids BASEMENT MEMBRANE Encompasses pericytes and endothelial cells closely adjacent to plasma membrane of astrocyte end feet,enclosing cerebral capillaries.

6. Tight junction Tight junction established by transmembrane proteins like : junctional adhesion molecule-1 , occludin and claudin 1,3,5 and 12-blocks paracellular route. Cytoplasmic accessory proteins like zonula occludens-1 and 2 ,cingulin,AF-6 –blocks or allows minimal transcellular route JUNCTIONAL ADHESION MOLECULE maintain tight junction properties. Claudin provides tight barrier capabilities Occludin and zonula occludens-1 regulates targeted signalling Early feature of BBB development is formation of tight junction seen in 14 weeks fetus also

7. Pericytes Enveloping brain microvessels and capillaries found in close proximity of astrocyte and neurons Plays critical role in formation and maturation of BBB by specific gene expression Covers 22-33% of endothelium Induce polarisation of astrocyte endfeet surrounding CNS blood vessel In absence of pericytes – abnormal vasculogenesis,endothelial hyperplasia and increased permeability of brain is seen.

8. Astrocytes Releases soluble substances to synthesize more transmembrane proteins Interacts with pericytes and microvascular endothelial cells by endfeet protrusion ensheathing capillaries Maintainance of BBB in homeostasis of extracellular concentration of transmitters,metabolites,ions and water Interaction between astrocytes and neurons determine synaptic transmission In tumor no astrocytes seen there is tight junctions seen.

9. Tight junction restricts diffusion of polar solutes through intercellular cleft. Barrier permeable to lipid soluble substance: Caffeine Nicotine ethanol Also gases like o2 , CO2,He,Xe passes Transfer of multidrug transporter limit concentration within CNS

10. AQUAPORINS are for water homeostatsis AQP1 seen in epithelial cell in choroid plexus AQP4,5 and 9 are localized on astrocytes and ependymal cells

11. Controlled movements by transporters : efflux and nutrient transporters Endothelial cells of brain expresses insulin independent glucose transporter GLUT1 GLUT1 plays vital role in brain glucose upregulation during starvation and hypoxia BBB impermeable against amino acids like aspartate and glutamate.But levodopa interacts with facilitative amino acid transporter L1 BBB is also impermeable for high concentrated drugs,so several strategies has been incorpated to overcome this obstacles

12. Strategies overcome BBB Directed into CSF Use of vasoactive compounds Higher lipidsolubility drugs Endogenous transport modification Blocks efflux transport

13. Disease breach BBB ENCEPHALITIS MULTIPLE SCLEROSIS BRAIN TRAUMA ALZHEIMER’S DISEASE EPILEPSY STROKE TUMORS

14. CRANIAL NERVES 1.OLFACTORY NERVE 2.OPTIC NERVE 3.OCCULOMOTOR NERVE 4.TROCHLEAR NERVE 5.TRIGEMINAL NERVE Opthalmic Maxilla Mandible 6.TROCHLEAR NERVE 7.FACIAL NERVE 8.VESTIBULOCOCHLEAR NERVE 9.GLOSSOPHARYNGEAL NERVE 10.VAGUS NERVE 11.ACCESSRY NERVE 12 GLOSSOPHARYNGEAL NERVE