BBB

• What are the different types of BB interfaces ?

  • BBB
  • BCSF
  • Ependymal
  • Meninges
• BBB are located at the vessel walls
• The meninges are made up of dura, arachnoid, and pia matter
• BBB allow molecular transit to be bidrectionnal and have different transporters : this is called selective permeability
• What are the main functions of BBB ?

  • neuroprotction against substances and pathogens
  • Transport of nutrients
  • Ionic homeostasis
• What are the structures without BBB meaning they have direct connection with blood (here the 2 main groups) ?

  • CVO = circumventricular organs
  • Secretory organs
• What are the 3 regions of CVO (circumeventricular organs) ?

  • Sub fornical organ
  • Organsu vasculum OVLT
  • Area postema AP
• What are the 4 regions of secretory organs ?

  • Pineal
  • neurohypophyse
  • medial eminence
  • subcommissural organ SCO
• Ependymal cells are the lining of the ventricles of brain and they do NOT have tight junctions TJ
• BCSF are located at the ventricular system
• What are the functions of BCSF ?

  • Neuroprotection
  • Detox and antioxidant
  • Production of CSF
  • Sentinel function and neuroimmune regulation
  • Secretion of GF
• What BBB types of cells you have ?

  You can have endothelial cells and astrocyte endfeet
• What BCSF types of cells you have ?

  You can have epithelial and endothelial cells. Plus the brain parenchyma has ependymal cells.
• The dura matter has lymphatic vessels
• The only matter that does NOT have TJ is the pia matter
• What is the perivascular plase ?

  It is where CSF mixes with the interstitial fluid
• If i have a neurdegenerative disease, what kind of issue do I have with my BB interfaces ?

  • have dysregulated lipid metabolism with P-glyc and LDL receptor taht don't work= like in AD
  • have disruption of BBB = like in PD
  • issues with BCSFB = like in aging and AD
• The BCSFB is also reffered to as choroid plexus
• If i have a cognitive disease, what kind of issue do I have with my BB interfaces ?

  • non brain tumors
  • Immune system activation
  • increased permeability like in TBI
  • Preeclampsia aka increased blood flow
• If i have a neurodevelopmental disease, what kind of issue do I have with my BB interfaces ?

  • non obstructive hydrocephalus aka when you have excessive CSF
• What are the two factors that can cause excessive CSF secretion ?


  Cytokine expression and SPAK phosopho-activation
• xenobiotic transporters are transporters responsible for chemical uptake into cells
• What molecules maintain immune quiescence ?

  Quiescence is maintainted because of proteins like P-secretin, atypical chemokine Rc 1 and matrix metalloprotein.
• Why molecules can maintain quiescence ?

  Because basically they are not expressed constitutively in microvascular endothelial cells or perivascular cells = no immune cell can cross barrier
• What happens in the immune system is activated ?

  • expression of p-selectin + other molecules
  • facilitates adhesion and transmigration of immune cells
• Only 2% of drugs can actually acess the CNS
• What are the 2 ways for a molecule to enter the brain ?

  • if its hydrosoluble = thanks to TJ = paracellular route
  • if its liposoluble = thanks to transporters and Rc-mediated transcytosis = transcellular routes
• Paracellular route is for hydrosoluble molecules
• Transcellular is for liposoluble molecules
• Efflux transporters carry liposoluble substances from brain to blood
• What are the two types of efflux transporters ?

  • ABC
  • SLC
• What does the efflux transporters absolutely need ?

  ATP
• Are efflux mechanisms the same between the 2 BB interfaces ?

  NO
• WHat are the drugs that can be carried with ABC ?

  • anticancer drugs
  • antibiotics
  • anticonvulsants
  • antidepressants
  • analgesic
• What are the drugs that can be carried with SLC especially OAT (organic anion transporter) ?

  • macromolecular drugs like antibodies aka immunoglobulin G
  • some anticancer drugs like azidothymidine
• How to assess penetration of drug ?

  With lumbar cerebrospinal fluid sample
• What is a lumbar puncture ?

  It is the collection of CSF from subarachnoidal space
• How to improve drug delivery ?

  • Intrathecal injection
  • FOR SMALL drugs = block efflux transporters or design liposoluble drugs that are not recognized by them
  • FOR LARGE drugs = favorise the transcytosis or microbubble + ultrasound injection
• How to improve large drugs specifically ?

  • favorise transcytosis
  • Focused ultrasound coupled to microbubble injection