CVB 2015
| Name | Place | Description of Interests | Status of Discussion | |
| Pierre Olivier, organizer | Paris | pierre-olivier.couraud@inserm.fr | No contact | |
| Nicola Marchi (Luca’s friend) | Montpellier, France | Nicola.Marchi@igf.cnrs.fr | No contact | |
| Lester Drewes (Organizing committee) | U Minn (organizing committee | ldrewes@d.umn.edu | exosome islation from plasma | No contact |
| Yuri Persidsky | Temple Univ., PA | yuri.persidsky@tuhs.temple.edu | No contact | |
| Jane Alder | UK | jealder@uclan.ac.uk | No contact | |
| Imola Wilhelm and Istvan A. Krizbai | Hungary | krizbai.istvan@brc.mta.hu | They reached out to Tejas and he responded 7/28 | |
| Maria Deli | Hungary | deli.maria@brc.mta.hu | Hungary, Member of Consortium | Jim wrote 7/29 |
| Britta Engelhardt | Switzerland | bengel@tki.unibe.ch | Jim wrote 7/29 | |
| Mouhssin Oufir | Switzerland | mouhssin.oufir@unibas.ch | ||
| Fruzsina Walters (competitors!) (PhD Student) | Hungary | walter.fruzsina@brc.mta.hu | LOC BBB device | Jim wrote 7/29 |
| Piotr Siupka (Post Doc) | Denmark | siupka@biomed.au.dk | ||
| Paula del Rey Puech (Edelman lab, MIT) | MIT | pauladrp@mit.edu |
Conference Notes
June 6
first visualization of bbb
reese and karnovsky 1967; brightman and reese 1967
transcytosis is less; less rate
BBB detected by injecting dextran, hoechst etc
possible hypothesis: percityes control endothelial cells to secrete factor responsible for increasing transcytosis
Virgintino, talk # 3
cell-cell communication: tunneling nano tubes (TNT)
David Atwell plenary talk
conventional thought: SMC contain vascular diameter
pericyte: put processes around the vessel in brain and heart as well
pericyte constriction is calcium dependant
signals pass across adjacent pericyte; they have long processes, almost touch other
vasodilatory sigmals like prostaglandin from neurons activate pericytes to start their vasodilation processes
Capillaries dilate before arteriole; also more prominently near pericytes
SMC are more controlling in thicker vessels: veins n arterioles
Pericytes could be for small and mid capillaries
PERICYTES: Spatially separated somata is fundamental characteristics, even if seen in the stage of transition to SMCs : main definition!!
Post ischaemia: pericytes constrict capillaries (calcium dependant, massive rise in calcium) and die!
pericytes die when endothelial cells remain unaffected after stroke
Day 2: Plenary talk- Elisabetta Dejana
endothelial cells highly heterotypic
altered junctional integrity not only affects vascular stability but also intracellular signalling and other pathologies
cerebral cavernous malformation: vascular disease of CNS: leaky and prone to hemorrhage–stoke seizures etc
sporadic vs familial CCM
endothelial polarization affects lumen behavior
podocalyxin: apical side protein of EC in normal vessel
vascular malformations in the retina of CCM-EC KO mouse: junction dismantled
Loss of CCM1 induces endothelial to mesenchymal transition (EMT)
CCN null->vein enlargement->single lesion->mulberry lesion
junction dismantling->beta catenin-> EMT->->-> inflammation-> death
Day 3 – Plenary talk- U Dirnagl
Stroke-> only clinically useful- IV thrombolysis
inflammation can also act protective for brain post-stroke
athero->peripheral inflammation->secondary lesion growth->(immunodepression)infection, autoimmunity->Bad outcome!
OR
athero->brain inflammation->containment, repair, regen.->protective immunity->good outcome!
acute inflammation causes neurons, astrocytes release toxic stuff like radicals, cytokines->affects ECs->BBB loss
delayed response->adaptive immune system kicks in!
bad epitopes circulating in brain due to BBB loss can activate t cells
further delayed phase: immunodepression and infection->pneumonia
Intra-parenchymal invasion of neutrophil … or may be not-> controversial issue!
macrophages could prevent hemorrhagic transformation after stroke
pharmacological ablation of microglia increases infarct volume
accepted notion+ inflammation is followed with repair; not always; nude mice without PMN and macrophages had perfect wound repair
Opposite of Seok et al on PNAS mouse paper->genomic responses in mouse models greatly mimic human inflammatory diseases PNAS 2014
Alzheimer’s- Talk 1
ABETA42 is bad, ABETA 38 is good/normal
Gamma secretase!
NSAID Flurizan could not cross BBB
Use nanoparticles for drug delivery
LDL receptor-related protein – LRP can treat alzheimer’s
Drug delivery talk-2 Integrative optical imaging (IOI)
extracellular space is very small and tortous with gaps of 40-60 nm; diffusion barriers
“Flow follows along the course of blood vessels in perivascular spaces”
Nedergaard=>”Glymphatic pathway”
Intracisternal infusions
Day 4
Talk 1: Coagulation activity in CNS as a imaging biomarker for innate immune activation and neurodegeneration
BBB disruption-> innate immunity -> antigen presentation And ROS generation -> M. Sclerosis
Fibrin deposition responsible for many neurologic disease
Talk 3: brain has very few native immune cells
In MS, most commonly infiltrate- CD4 and CD 8 T cells; macrophage and DCs
Talk 4: trans endothelial mig. for t cells = “autotaxin”