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BLOOD BRAIN
BARRIER
DR.ABHINAV KUMAR
M S RAMAIAH MEDICAL COLLEGE,BANGALORE
ANATOMY OF BLOOD BRAIN BARRIER
Brain Microvessels
1. Endothelium with 3 structural features
a. tight intercellular junctio...
CARRIER FUNCTION
• nutrients to the brain and the removal of metabolites
• – Small lipid soluble molecules and blood gases...
BBB v/s capillaries of peripheral nerve +
organs
Characteristic or structure BBB capillaries
Tight junction resistance 5-1...
Circumventricular organs
Areas of the brain where the BBB is weak, & allows substances to cross
into the brain somewhat fr...
• Subfornical organ-chemoreceptive area monitoring blood
angiotensin II level
• Important for the regulation of body fluid...
ENDOTHELIAL CELLS
• Form a continuous sheet covering the surface of capillaries
• – Inter-connected by TIGHT JUNCTIONS (x5...
PERICYTES
• Endothelial cells are sitting on the basal membrane– engulfed in basal
membrane are the pericytes
– Derived fr...
FUNCTIONS OF BBB
Ion regulation
• Stable environment for neural function
• combination of specific ion channels and transporters keeps the ...
Neurotransmitters
• Blood plasma contains high levels of the neuroexcitatory amino acid
glutamate which fluctuate signific...
Macromolecules
• BBB prevents many macromolecules from entering the brain.
• The protein content of CSF is much lower than...
Neurotoxins
• Protective barrier which shields the CNS from neurotoxic substances
circulating in the blood.
• Neurotoxins ...
Brain nutrition
• low passive permeability to many essential water- soluble nutrients
and metabolites required by nervous ...
–
Routes across the BBB
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BLOOD BRAIN BARRIER

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blood brain barrier anatomy,physiology,function,and association with diseases

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BLOOD BRAIN BARRIER

  1. 1. BLOOD BRAIN BARRIER DR.ABHINAV KUMAR M S RAMAIAH MEDICAL COLLEGE,BANGALORE
  2. 2. ANATOMY OF BLOOD BRAIN BARRIER Brain Microvessels 1. Endothelium with 3 structural features a. tight intercellular junctions without fenestrations b. paucity pinocytic intracellular vesicles relative lack of vesicular transport c. abundant mitochondria Basement membrane -surrounds endothelium -40-50 nm thick proteoglycans, heparin sulfate, lamnin,entactin & type IV collagen 2. Pericytes with smooth muscle- like properties that reside adjacent to capillaries 3. Astroglial process –ensheath >95% of the abluminal vessel surface
  3. 3. CARRIER FUNCTION • nutrients to the brain and the removal of metabolites • – Small lipid soluble molecules and blood gases like O2 and CO2 diffuse passively through the BBB while essential nutrients like glucose and amino acids require specific transport proteins in order to reach the brain
  4. 4. BBB v/s capillaries of peripheral nerve + organs Characteristic or structure BBB capillaries Tight junction resistance 5-10 ohm/sq.cm 2000 ohm/ sq.cm Fenestration/clefts no yes Vesicular transport deficient abundant Pinocytic vesicles rare abundant Mitochondria abundant rare Tight junction ++++++ + Selective transport ++++++ - Astrocyte foot process ++++++ -
  5. 5. Circumventricular organs Areas of the brain where the BBB is weak, & allows substances to cross into the brain somewhat freely are known as "circumventricular organs. • Leaky regions are isolated from the rest of the brain by specialized ependymal cells called tanycytes located along the ventricular surface close to the midline • Pineal body • Secretes melatonin and neuroactive peptides. Associated with circadian rhythms. • Neurohypophysis (posterior pituitary) • Releases neurohormones like oxytocin and vasopressin • Area postrema • "Vomiting center": when a toxic substance enters the bloodstream it will get to the area postrema and may cause the animal to throw up
  6. 6. • Subfornical organ-chemoreceptive area monitoring blood angiotensin II level • Important for the regulation of body fluids. • Vascular organ of the lamina terminalis • A chemosensory area that detects peptides and other molecules. • Median eminence • Regulates anterior pituitary through release of neurohormones.
  7. 7. ENDOTHELIAL CELLS • Form a continuous sheet covering the surface of capillaries • – Inter-connected by TIGHT JUNCTIONS (x50-100 tighter than periphery) – form belt like structure at the apical region of the cells
  8. 8. PERICYTES • Endothelial cells are sitting on the basal membrane– engulfed in basal membrane are the pericytes – Derived from the Greek word“kytos”(hollowvessel), pericytes surround small vessels. – Cover 22-32% of endothelium – regulation of endothelium proliferation,angiogenesis & inflammatory processes – Regulate BBB specific gene expression patterns in endothelial cells – Induce polarisation of astrocyte endfeet surrounding CNS blood vessels – In the absence of pericytes - an abnormal vasculogenesis, endothelial hyperplasia and INCREASED permeability in the brain
  9. 9. FUNCTIONS OF BBB
  10. 10. Ion regulation • Stable environment for neural function • combination of specific ion channels and transporters keeps the ionic composition optimal for synaptic signalling function. • concentration of [K+] in mammalian plasma is approximately 4.5 mM, but in CSF and brain ISF –> ∼2.5–2.9 mM, in spite of changes that can occur in plasma [K+] following exercise or a meal, imposed experimentally, or resulting from pathology • Ca2+, Mg2+ and pH are also actively regulated at the BBB and BCSFB
  11. 11. Neurotransmitters • Blood plasma contains high levels of the neuroexcitatory amino acid glutamate which fluctuate significantly after the ingestion of food. • If glutamate is released into the brain ISF in an uncontrolled manner, as for example from hypoxic neurons during ischemic stroke, conside- rable and permanent neurotoxic/neuroexcitatory damage can occur to neural tissue. • Since the central and peripheral nervous systems use many of the same neurotransmitters, the BBB also helps to keep the central and peripheral transmitter pools separate, minimising ‘cross- talk’
  12. 12. Macromolecules • BBB prevents many macromolecules from entering the brain. • The protein content of CSF is much lower than that of plasma • Plasma proteins such as albumin, pro-thrombin and plasminogen are damaging to nervous tissue, causing cellular activation which can lead to apoptosis • Thrombin and plasmin if present in brain ISF can initiate cascades resulting in seizures, glial activation, glial cell division and scarring, and cell death • Leakage of these large molecular weight serum proteins into brain across a damaged BBB can have serious pathological consequences. • Cystatin-C
  13. 13. Neurotoxins • Protective barrier which shields the CNS from neurotoxic substances circulating in the blood. • Neurotoxins may be endogenous metabolites or proteins, or xenobiotics ingested in the diet or otherwise acquired from the environment. • A number of ABC energy-dependent efflux transporters (ATP-binding cassette transporters) actively pump many of these agents out of the brain .
  14. 14. Brain nutrition • low passive permeability to many essential water- soluble nutrients and metabolites required by nervous tissue. • Specific transport systems to ensure an adequate supply of these substances. • differentiation of the endothelium into a barrier layer begins during embryonic angiogenesis and in the adult is largely maintained by a close inductive association with several cell types, especially the end feet of astrocytic glial cells.
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  16. 16. Routes across the BBB

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