Lecture 6

• Blood-Brain Barrier (BBB)


  The brain and the spinal cord are protected from the general circulation and the body
• Blood-Brain Barrier (BBB)


  • The ionic composition of the extracellular fluid around the neuron must be carefully controlled
  • Can not change the excitability of the membrane
  • Can not have neurotransmitters floating around for no reason
• Blood-Brain Barrier (BBB)


  The extracellular fluid in the neuronal environment (brain and spinal cord) are carefully regulated through Blood-Brain Barrier (BBB)
• Blood-Brain Barrier (BBB)


  A 2-fold entity: Between Blood Vessels & Interstitial Fluid and Blood Vessels & CSF
• Parkinson's disease

  
• Areas Lacking the BBB

  • Most of the brain is protected by BBB, but it is not continuous
  • At some places it is essential for neurons to communicate freely with the blood stream (e.g. hypothalamus)
  • The pituitary gland (releases hormones) is directly connected to the hypothalamus > thus, BBB is purposely broken to allow release of hormones
  • In 'Circumventricular organs' (around 3rd ventricle) the BBB is broken so neurons can sense specific chemical [ ]
  • Generally, BBB is broken in areas that interact with endocrine system or require sensitivity to metabolites in plasma
• Meninges


  • Dura mater (very tough membrane, sac containing the brain and the spinal cord)
  • Arachnoid membrane (much more delicate tissue)
  • Pia mater (lies right on top of the brain; tethered to Arachnoid by Arachnoid 'Trabeculae')
  • Between the arachnoid membrane and Pia matter > Subarachnoid space (filled with CSF) > brain floats to protect from mechanical stress

  
• Reticular formation
• In the subarachnoid space, we have blood vessels > capillaries to the brain tissue > BBB, in between the capillaries and the brain tissue

  
• Blood Vessels


  • The endothelial lining of the BV, mostly contain large gaps (fenestrations), through which molecules can pass
  • In Brain, endothelial cells are tightly bound leaving no gaps > this constitutes the BBB (everything has to be transported)
• Ventricles


  • The ventricles are cavities deep inside the brain
  • A large curving Lateral Ventricle (LV) inside each cerebral hemisphere, a paired structure across the midline
  • The LV empties into the 3rd Ventricle, right in the middle, deep in the brain under the cerebral hemisphere
  • The 3rd Ventricle communicates via a channel called "Aqueduct of Sylvius" to the 4th Ventricle
  • From the 4th Ventricle, we have a canal, "Central Canal" which goes in the middle of the spinal cord
  • All these ventricles are filled with CSF
• CSF production and drainage

  1. CSF produced in the ventricle drains through the ventricle of the central canal

  2. CSF then moves to outer parts of the brain (subarachnoid space) and finally exits at the top of the brain into large venous sinus (on the midline)

  3. All the CSF eventually drains into either venous sinus or veins somewhere along the line

  4. About ½ CSF drains through 'Arachnoid villi' into the venous system
• Arachnoid Villi


  An out pouching of the arachnoid tissue, sticks out through the dura matter into the venous sinus > CSF drains into the venous system
• Ventricles


  • Ventricles are filled with CSF, which is the bathing medium of brain (highly regulated ionic content, few macromolecules)
  • CSF is produced from plasma by 'choroid plexus', which lines the ventricles (LV, 3rd, 4th, all have choroid plexus producing CSF)
  • All the ventricles are filled with CSF (including the subarachnoid space, there is communication between the ventricles and the subarachnoid space) and eventually drains into the venous system
• Choroid Plexus


  • Choroid Plexus produces most of CSF (but not all, some are produced in the capillaries inside the brain)
  • Made up of epithelial cells connected by tight junctions
  • Choroid Plexus produces CSF continuously (550 ml/day) to circulate cleansing mechanism
  • Choroid Plexus is a dense network of capillaries ballooning out into the ventricular wall with tight junction so that everything has to be transported
• Cerebrospinal Fluid (CSF)


  • CSF is produced by 'Choroid Plexus' in ventricles
  • CSF fills the ventricles and the subarachnoid space
  • CSF has same osmolarity and [Na+] as blood
  • Greatly reduced [K+], [Ca2+] and [Mg2+]
  • Total volume on an average person is 215ml
  • Cranial CSF is 140ml (25ml in ventricles, 115ml in subarachnoid space) and the spinal CSF is 75ml
  • Most of the CSF is in the subarachnoid space, serving as 'cushion'
• A lumbar puncture (spinal tap) is a diagnostic, therapeutic procedure > collect sample of cerebrospinal fluid (CSF) for analysis
• Astrocytes


  • The walls of the capillaries are plastered with the 'end feet' of glial cells, particularly the astrocytes
  • Astrocytes provide a bridge between neurons and blood vessels
• Astrocytes


  • Efficient at glycolysis
  • Produce lactate as an end-product
  • Lactate is a substrate for ATP production
• Astrocytes


  • Remove neurotransmitters
  • Provide energy substrates for neurons and more
  • Following and latching on to BV (some end feet latched onto the BV and the others with neurons)
• Local Blood Flow


  1. Astrocytes regulate local blood flow

  2. Astrocytes are bridging the gap between BV and neurons, so they are in good spot to signal BV when to dilate and to constrict (increase or decrease blood flow)

  3. Astrocytes have connection with the neuron at the synapse and when they detect increased signaling, they can send a metabolic signal outward to BV (opposite to nutrient flow), signaling neuronal activity level
• Local Blood Flow Regulation

  1. Glutamate in synapses triggers Ca2+ release within astrocytes; Ca2+ wave travels through astrocytes and triggers prostaglandin (PGE2) release at end-foot

  2. PGE2 causes vasodilation > increased blood flow