CVB Conference in Paris (July ’15)

ByJim

Program

C. Gu – Harvard

  • Seminal Experiments Reese and Karnolvsky 1967
  • Brightman and Reese (1969)
  • Two unique features of CNS endothelium: Specialized tight junctions – Very low rate transcytosis.
  • Tight Junction by EM Ben-Zvi et al 2014 Nature. Transcytosis becomes upregulated not tight junctions. 2-3x injection
  • HRP injection. Tracer containing vessels travel in endothelial cells
  • Inhibition of transcytosis is a major regulator of tight junction formation
  • Q. Ancient literature about vascular pressure rapidly producing vesicles

Virgintino

  • Tunnelling nanotubes, cell conversion ‘via cable’
  • Nanotubular highways for intercellular organelle transport – essential transport between distant cells. Clearly demonstrated in vitro in cancer cells.
  • Now demonstrated in tissue Chinnery, J Immunol 08 180:5779
  • She demonstrated in brain during development
  • Thinks TIP ECs require nanotubes
  • Pericytes

Role of connexion hemichannels and calcium dynamics in inflammation-induced blood-brain barrier failure ? (Speaker : L. Leybaert)

  • Lymphocyte migration across the BBB is Ca2+ dependent
  • Reportor dies 3kDa 10kDa 70 kDa De Bock et al, unpublished LPS as inflammatory trigger
  • All MW markers grow in permeability 3 hour 6 hour and 24 hours
  • Astrocytic laminin maintains blood brain barrier integrity by regulating brain pericyte differentiation (Y. Yao)
  • 95% coverage by astrocyte endfeed (mastison and colleagues ? 2010? )

Yao Yao – Astrocyte Laminin Maintains Blood Brain Barrier Integrity

  • Basement membrane – Pericytes are covered by the basement membrane. Laminin is the basement membrane – Aumailley, Cell Adh Migr, 2013
  • Cell Specific Isoforms Astrocytes and endothelial cells (Sixt JCB 2001)
  • Gamma 1 is unique to BBB(?)
  • Developed a conditional knockout Yao et al Nat Commun 2014

Contributions of Cell-Matrix-Interactions to the Functional Integrity of the Neurovascular Unit (J. Huppert)

  • Interstitial Space vs basement membrane – Interstitial matrix does not exist in the brain?

CSF-brain barriers – V. Prevot

  • Hypothalmus/Blood Barrier as an entry point for hormome regulation of the Brain
  • Fenestrated endothelium
  • Check out the fish nose as a flow through sensor

Day 2

Elizabeth Dejana

  • Phenotypic heterogeneity of endothelial cells – arteriol, venule, capillary, sprout, lymphatic, organ specific

R. Bendayan gets  from Pierre Courand and Scherrmann – source of brain microvessel endothelial cells

Intrathecal delivery of antibodies – perivascular flow and interstitial diffusion visualized by fluorescence imaging and MR (Speaker : R. Thorne)

Check out Thorne 2006 paper in PNAS for image of packed NVU. Diffusion space is 40-60 nm.

Needergaurd at Rochester published in science on CNS barriers

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