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Vascular Biology
 
October 26 - 30
Joao Laranjinha, Ana Ledo
Professors (from the School of Medicine, Kings College, London, UK):
Philip Aaronson
Paul Fraser
Giovanni Mann
 
Coordinators (from CNC):
João Laranjinha
 
Ana Ledo
 
 
General plan:
 
Day 0 (Tuesday, 27)
14:30H – Preliminary information
15:00H - Nitric oxide – the basics (Chemistry, Biochemistry, Biology)
(João Laranjinha)
16:00H – Dynamics of Nitric oxide in the brain
(Ana Ledo)
 
Day 1 (Wednesday, 28)
Endothelial Derived Hyperpolarizing Factor              
(led by Philip Aaronson)
 
Day 2 (Thursday, 29) 
Leukocyte Endothelial Interaction                                         
(led by Paul Fraser)
 
Day 3 (Friday, 30) 
Role of Oxygen Stress Related Genes in Cerebral Oedema
(led by Giovanni Mann)
 
Check below the detailed information for days 1-3, including the objectives, programme description, notes for the presentations, reading lists for presentations and timetable.
All papers are available as PDFs.

Training doctoral course on:
 
THE VASCULAR BIOLOGY UNDERLYING CEREBRAL OEDEMA
 
at Centre for Neurosciences and Cell Biology, Coimbra, Portugal
 
By Dr PA Fraser, Prof GE Mann & Dr PA Aaronson
 
School of Medicine, King’s College London.
 
 
 
A 3 day course 28th to 30th October 2009
 
Objectives
The aim is to introduce students to the concepts of regulation of the vasculature leading to its responses in the brain following an ischaemic incident. By the end of the course students will be familiar with the endothelial generation of nitric oxide and its role in vasodilatation, the current theories of endothelial-derived hyperpolarizing factor, the mechanisms by which leukocytes transverse an endothelial barrier and with current ideas on the mechanisms of the formation of cerebral oedema. This course will provide the students with transferrable skills in reading original scientific papers, producing coherent presentations an co-operative and critical discussion on the selected papers and subject area.
 
Programme description
This is a seminar-based course with introductory lectures. The lectures will be given at the beginning of each day, and the students will then give 10 to 15 minute PowerPoint presentations on original research papers. Each presentation will be followed by an open-ended student-lead discussion, which will be supplemented by comments and insights from the visiting experts. In addition, these experts will present a seminar based on their own research at the end of each day.
 
INTRODUCTORY LECTURES
1. Endothelial Derived Hyperpolarizing Factor (Dr. P.A. Aaronson)
2. Leukocyte Endothelial Interaction                  (Dr. P.A. Fraser)
3. Formation of Cerebral Oedema                     (Prof. G.E. Mann)
 
Student SEMINARS
PowerPointpresentations of four related papers on the above topics followed by discussion. Each student (12 in total) will present a paper in one of the following sessions. Each presentation will be supplemented by a discussion lead by two students who are advised to collude with the presenter beforehand with the aim of generating a good discussion. The visiting experts will help with this discussion. At the end of each session the experts will give constructive feedback on individual presentations and will be available for further discussion of points related to the session, or other aspects of their research. 

Notes on preparing PowerPoint Presentations
 
The seminars are aimed to help you learn the subject matter by having a good discussion on and around the topic outlined by the reading list. It is important that certain ground rules are observed so that your presentations are understood and enjoyed by your audience.
Each paper should be presented in terms of:- 
Aims The authors will have had to justify the reasons for carrying out their experiments, you should mention these and place the work into some context.
Methods The main methods should be very briefly outlined so that the audience can easily understand what really went on in the experiments. A simple diagram of the apparatus and/or the experimental procedures might be helpful, and is sometimes essential. Do not be over elaborate. The methods for individual experiments are often best presented with the result.
Findings The crux of the presentation. You should present carefully selected graphs, and possibly tables, to emphasise the points you (or the authors) wish to make. Any scientist publishing a paper realizes that the best way to get a message across is in terms of a graph, and often considerable care will have been taken in deciding how best to present the data. There is no need to present the full content of the paper, just those elements that you think are really important.
Discussion Have the authors achieved their declared objectives? Are there possible alternative interpretations of their results?  What is the net contribution to the subject of this piece of work?
You will appreciate that you have to know the papers to a considerable depth to be able to present them well. It is not the intention that you read your notes. It is far, far better that you talk fluently to the class, and refresh your memory from time to time by glancing at a crib sheet. In that way what ever you say will be part of a conversation, and allow your personality to come across. A reading will be dry and stilted, far removed from ordinary human expression. 
Questioners
You must of course read the paper first! Your questions should be based on whether you think that the authors have really shown what they have claimed, could there be other alternative explanations for their results, and even suggest a better experiment. You are encouraged to collaborate with the presenter and the others with an aim to generate as good a discussion as possible. 
 
 
The 12 students will present the numbered papers on the reading lists below. For the sake of convenience I have labelled the students from A to L.
 
Journal Paper
Presenter
Student Questioner 1
Student Questioner 2
1
A
I
H
2
B
J
G
3
C
K
F
4
D
L
E
5
E
A
L
6
F
B
K
7
G
C
J
8
H
D
I
9
I
E
D
10
J
F
C
11
K
G
B
12
L
H
A
 
So that the student presenting paper 1 will ask questions on papers 5 and 12 etc.
 
Timetable
 
Wednesday 28th October
10.00 Introductory Remarks  (PF )
10.05 Lecture “The nature of EDHF”  (PA)
10.45 Student presentations of papers 1 & 2
12.15 Lunch                                                                                       
14.00 Student presentations of papers 3 & 4    (PA)
15.30 Research Seminar : “Hypoxic Vasoconstriction”  (PA)
 
Thursday 29th October
10.00 Lecture “Passage of Leucocytes across the Endothelium” (PF)
10.45 Student presentations of papers 5 & 6
12.00 Lunch
13.30 Student presentations of papers 7 & 8
15.00 Research Seminar : “Does NO regulate Vascular Permeability” (PF)
 
Friday 30th October
09.00 Lecture “Processes of Cerebral Oedema Formation” (GM)
09.45 Student presentations of papers 9, 10,11 & 12
11.00 Concluding Remarks
11.30 Research Seminar
“Transcription Factors in Neurovascular Unit Protection” (GM)
 
 
Endothelial Derived Hyperpolarizing Factor
 
Review: EDHF: an update. (2009) Félétou M, Vanhoutte PM. Clin Sci (Lond). 117:139-155
 
1. Mather S, Dora KA, Sandow SL, Winter P, Garland CJ. (2005) Rapid endothelial cell-selective loading of connexin 40 antibody blocks endothelium-derived hyperpolarizing factor dilation in rat small mesenteric arteries. Circ Res. 97(4):399-40
2. Fleming I, Rueben A, Popp R, Fisslthaler B, Schrodt S, Sander A, Haendeler J, Falck JR, Morisseau C, Hammock BD, Busse R. (2007) Epoxyeicosatrienoic Acids Regulate Trp Channel Dependent Ca2+ Signaling and Hyperpolarization in Endothelial Cells. Arterioscler Thromb Vasc Biol. 27:2612-8.
3. Dora KA, Gallagher NT, McNeish A, Garland CJ. (2008) Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries. Circ Res. 102:1247-1255
4. Köhler R, Heyken WT, Heina P, Schubert R, Si H, Kacik M, Busch C, Grgic I, Maier T, Hoyer J.(2006) Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler Thromb Vasc Biol. 26:1495-1502
 
Leukocyte - Endothelial Cell Interactions
 
Review: Ley K, Laudanna C, Cybulsky MI, Nourshargh S. (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 7:678-689
 
5. Huang AJ, Manning JE, Bandak TM, Ratau MC, Hauser KR, Silverstein SC (1993) Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J Cell Biol 120: 1371-1380
6. Thompson RD, Noble KE, Larbi KY, Dewar A, Duncan GS, Mak TW, Nourshargh S. (2001) Platelet-endothelial cell adhesion molecule-1 (PECAM-1)-deficient mice demonstrate a transient and cytokine-specific role for PECAM-1 in leukocyte migration through the perivascular basement membrane. Blood. 97(6):1854-1860
7. Woodfin A, Voisin MB, Imhof BA, Dejana E, Engelhardt B, Nourshargh S. (2009) Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood. 113:6246-6257
8. Carman CV, Sage PT, Sciuto TE, de la Fuente MA, Geha RS, Ochs HD, Dvorak HF, Dvorak AM, Springer TA. (2007) Transcellular diapedesis is initiated by invasive podosomes. Immunity. 2007 Jun;26(6):784-97
 
Cerebral Oedema
Review: Improving outcome after stroke: overcoming the translational roadblock. (2008) Endres M, et al., . Cerebrovasc Dis. 25:268-278
 
9. O Donnell ME, Lam TI, Tran LQ, Foroutan S, Anderson SE. (2006) Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion. J Cereb Blood Flow Metab. 26:1234-1249
10. Kahles T, Luedike P, Endres M, Galla HJ, Steinmetz H, Busse R, Neumann-Haefelin T, Brandes RP. (2007) NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke.38:3000-3006.
11. Hu DE, Easton AS, Fraser PA. (2005) TRPV1 activation results in disruption of the blood-brain barrier in the rat. Br J Pharmacol. 146:576-84.
12. Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A, Katakowski M, Lu M, Chopp M. (2005) Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab. 25:281-290
 
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