This Is MS Multiple Sclerosis Community: Knowledge & Support

Dr. Cooke: Humans never fully recover endothelium after vascular treatment or stenting (based on arterial interventions)

Dr Cooke,
Venous angioplasty and stenting reduced fatigue symptoms for 1year. Not a randomized trial.
Endothelium…lining of blood vessel
Hypothesis altered cerebrovenous hemodynamics in ccsvi predispose to ms pathobiology
Alteration in hemodynamic can cause permeability to the endothelium
Thickening of vessel wall. Perivenular cuffing infiltration of inflammatory cells, RBC egress and hemosiderin deposition
The endothelium maintains vascular homeostasis it is the Teflon coating of our blood vessels.
Release NO which causes vasodilation. Blood vessels can adapt to flow and regulate its diameter. The blood flow is entirely dependent on the endothelium. The endothelium can sense changes in the blood flow.
Disturbed flow happens at bends, branches and bifurcations.
Endothelial biology is altered by flow patterns
Role of endothelial adhesion molecules and disturbed flow. If you have disturbed venous flow the endothelium becomes more adhesive(like Velcro) and sets the person up for inflammation.
Ccsvi causes abnormal venous flow
External compression of a blood vessel can cause disturbed blood flow
Ccsvi changes venous flow and pressure and effects the endothelium and causes the endothelium to become like Velcro. This becomes attractive to white blood cells and causes inflammation.
Has submitted grants to NIH et al and has been turned down for CCSVI.
Changes in flow can change the endothelium. The endothelium in the brain is very different than the endothelium elsewhere…it’s very tight
Needs funding for more animal models.

Can diet help the endothelium? Not sure but omega 3, micronutrients helps with arteries, but we haven’t studied the veins

Dr. Cooke and Dr. Dake’s research was just published as a retrospective. This included the first patients treated at Stanford in 2009. There were large collateral channels in most of the pwMS seen at Stanford. The average patient had an 80% stenosis, which was reduced to 0% after stenting. The paper was delayed a year, due to political factors, but it is published now.

The endothelium is a single layer of cells, and it exerts control over circulating blood elements. Changes in venous flow and pressure can set up cerebral inflammation. increased strain increases endothelial cell (EC) adhesion molecules, EC chemokines, EC permeability, vein wall thickening, perivenular cuffing, oxidative stress, local hypoxia and plaque formation.

Dr. Cooke likes to say, “One is as old as one’s endothelium”---
The endothelial cells regulate vessel tone and the force of blood flow causes sheer stress, EC cells like blood flow. Blood vessels adjust to flow, changing diameter size. Flow mediated vasodilation is completely mediated by the endothelium. Structural changes of blood vessels long term. Endothelial cells line up in response with flow and hemodynamics.

There is disturbed blood flow in bends and arches of blood vessels--like an eddy in a river. Plaque forms in these areas where EC are exposed to abnormal flow. Platelets adhere to EC cells at bends, branches and bifurcations. Disturbed venous pressure--creates more adhesion, more inflammation is responding.

Zamboni’s evidence looked at how venous disease in the legs is like MS---venules in skin of venous insufficiency. Low shear stress starts epigenetic activation, which is causing thickening of vessel wall.
Smooth muscle cells are increased. CCSVI changes venous flow patterns, and creates hemodynamic alterations. White blood cells are attracted to endothelial adhesiveness.

Dr. Cooke would like his lab to study the endothelial cells in CCSVI. He would also like to create animal models of CCSVI beyond the mouse model. He has applied to all his previous sources to fund his research (like the NIH) He also applied to the MS Society, but this is the first time in his career he has been turned down. Controversy is keeping money away from this. We need funding to investigate this hypothesis.