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IMS: Neuroanatomy > Blood Brain Barrier > Flashcards

Blood Brain Barrier Flashcards

1
Q

Blood Brain Barrier

Definition

A

A layer of cells that seperates the peripheral fluids (blood) from the intercellular spaces in the brain.

Regulates the movement of molecules into and out of the nervous system.

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2
Q

BBB

Clinical Significance

A
  • Restricts access of the nervous system.
    • Microorganisms and Ab’s are normally excluded.
  • Creates unique extracellular environment required for nervous system function.
  • Attenuates or prevents the brain’s reaction to peripheral disturbances:
    • Hydration
    • Electrolyte balance
  • Obstacle to drug delivery to the brain
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3
Q

Brain Blood Suppy

A
  • Main routes:
    • Internal carotid arteries
    • Vertebral arteries
  • Venous drainage via dural sinuses ⇒ internal jugular vein
  • ~ 12 m2 of circulatory system surface in brain parenchyma
  • No neuron > 100 microns from a blood vessel
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4
Q

BBB

Structure

A

Two components:

  • Barrier between CNS vasculature and brain parenchyma.
  • Barrier between CNS vasculature and CSF.
    • Blood-CSF barrier
  • Function derived from:
    • structural & cytological properties of cerebral microvasculature
      • capillary endothelial cells
      • basement membrane
    • glial cells surrounding blood vessels in the brain
      • astrocytes with end feet
      • pericytes
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5
Q

Nervous System

Endothelial Cells

A
  • Continuous layer joined by tight junctions
    • Occludins block:
      • paracellular protein movement
      • hydrophilic transfer
      • ionic diffusion
    • Cut off size for an ionized soluble compound to pass is 180 daltons (~AA size)
  • Transcellular movement via endocytosis or receptor-medicated transport g_reatly reduced_
  • High density of mitochondria to support active transport
  • 1/3 thinner ⇒ higher risk for hemorrhage
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6
Q

Astrocytes

A
  • Can induce capillary endothelial cells to form and maintain BBB
  • Have processes with “end feet” which covers over 95% of capillary endothelial outer surface
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7
Q

Pericytes

A

Phagocytic microglial cells.

  • Stimulates endothelial cell proliferation
  • Regulates vessel contractility
  • Closes up holes when there is a breach
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8
Q

Endothelial Basement Membrane

A
  • Main components:
    • laminin
    • fibronectin
    • tenascin
    • collagens
    • proteoglycans
  • Contributes to exclusion of molecules movement due to net charge
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9
Q

Mechanisms of Transport

Across BBB

A
  • Diffusion
  • Facilitated diffusion
  • Active transport and ion exchange
  • Receptor-mediated transcytosis
  • Transcytosis via P-glycoprotein
  • Diapedesis
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10
Q

Diffusion

A

Passage through the membrane.

  • Small inorganic molecules highly permeable
    • Ex. gases: O2, CO2, NO, H2O
  • Lipophilic substances
  • Two non-polar molecules with high diffusion rates through BBB:
    • nicotine
    • ethanol
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11
Q

Facilitated Diffusion

A

Concentration-dependent.

Energy-dependent.

Saturable.

  • Amino acid transporter
    • Different ones for neutral, basic, or acidic AA
    • Ex. L-system for leucine and phenylalanine
      • Sodium dependent
  • Glucose transporter: GLUT-1
    • Found on luminal and adluminal endothelial cell membranes
    • Exits in neuronal and astrocytic membranes
  • Monocarboxylates
    • Lactate, pyruvate, acetate, SCFA, salicylic acid, nicotinc acid, some 𝛽-lactam Abx
  • Hexose amines
    • glucosamine, glutathione
  • Nucleosides
    • Adenosine, guanosine
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12
Q

Active Transport

&

Ion-Exchange Systems

A

Concentration-independent.

Energy dependent.

Saturable.

  • Vitamins
    • Entry limited when blood levels abnormally high
  • Na/K-ATPase
  • Neutral amino acids
    • “A” system
      • alanine, glutamine, histadine
    • “ASC” system
      • serine, cysteine
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13
Q

Receptor-Mediated Transcytosis

A

Similar to pinocytosis but required receptor activation.

  • Transferrin
  • Insulin
  • Leptins
  • IGF-I and IGF-II
  • Angiotensin II
  • Albumin
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14
Q

Transcytosis via P-glycoprotein

A

ATP-dependent Flippase

Member of the multi-drug resistance (MDR) protein family.

  • Transports back into the blood a variety of molecules that enter ECs or brain.
  • Typically organophosphate substrages:
    • Anti-neoplastic agents
    • Immunosuppresive drugs
    • Abx
    • Digoxin
    • Pesticides
    • Protease inhibitors
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15
Q

Diapedesis

A
  • Certain cells can break tight junctions and move between endothelial cells
    • Activated T cells, monocytes, and macrophages
      • But not unactivated ones
    • Metastatic cells
  • Not influenced by specific Ag, MHC, or T-cell type
  • Exits CNS unless specific Ag recognized
  • Some leave via lymphatic drainage
  • Can induce astrocytes and miroglia to present MHC:peptide
  • Can induce BBB breakdown
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16
Q

Blood-CSF Barrier

A
  • Exists at the choroid plexus of lateral and 4th ventricles
    • Sites of CSF production
    • Develops from invagination of neuroepithelial wall
      • Penetrated by capillaries of choroid arteries
  • Concentrations of Na, K, Mg, Cl, Ca, H, bicarb, glutamate, and others held at steady state in CSF and brain extracellular fluids
  • Endothelial cells of blood vessels in choroid plexus do no have tight junctions
  • Rather, there are apical tight junctions on neuroepithelial cells of chroid plexus surrounding capillary structures
17
Q

Other Barriers

A

Tight junction-based barriers exist wherever vascular system abuts CNS.

  • Blood-Labyrinth barrier
  • Blood-nasal mucosa barrier
  • Blood-retinal barrier
  • Blood-nerve barrier
18
Q

Places Lacking

BBB

A
  • NMJ and other peripheral axon terminals
  • Barrier around dorsal root ganglia
  • Circumvenricular organs:
    • Examples:
      • neurohypophysis
      • pineal gland
      • median eminence
      • area postrema
      • subfornical organ
      • organum vasculosum of lamina terminalis
    • Neurons in these regions needed to release into the blood or detect specific blood contents
    • Tanycytes line ventricular surface near these areas
      • have tight junctions
      • generally prevents free fluid exchange with CSF
19
Q

Methods of CNS Exit

A
  • Membrane diffusion
  • Saturable transport systems
    • Na-dependent AA co-transporters
    • Lactate and other metabolic products
  • Lymphatic drainage
    • meninges form a perivascualr sheath around larger vessels
    • demarcates the Virchow-Robin spaces
  • P-glycoprotein CSF reabsorption
20
Q

CSF Bulk Flow

A

In an average human:

  • 150 ml CSF
    • 80% in subarchnoid space
  • replaced ~ 4x per day at a rate of 500 mL/day
  • creates a “sink effect”
    • difficult for microorganisms to move up CSF flow
  • Flow from subarachnoid space ⇒ dural sinuses via arachnoid granulations
21
Q

Disorders Involving

BBB

A
  • Trauma
  • Vascular dysfunction
    • cerebral ischemia
    • HTN
    • VEGF increased at injury sites ⇒ increaes capillary permeability via NO
  • Infection
    • Some neuroinvasive microorganisms can cross BBB
    • Encephalitis
      • entry through BBB endothelium
    • Meningitis
      • entry through meninges
  • Age
  • Autoimmune disorders
    • MS
  • Alzheimer’s disease
    • Beta-amyloid peptide allowed to enter brain
    • Leads to amyloid angiopathy and formation of amyloid plaques
  • Epilepsy
    • increased pinocytotic activity during seizures
  • Prolonged stress

IMS: Neuroanatomy (23 decks)

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