Hi Bob-
This Adams paper from 1988 is a great one! It was one of the ones which helped me understand endothelial dysfunction in MS and how it related to Dr. Zamboni's discovery of extracranial venous blockage. We discussed it here in '09
http://www.thisisms.com/forum/chronic-c ... c8185.html
In the late 1980s, there not a complete understanding of how the endothelium and nitric oxide contributed to coagulation, blood brain barrier permeability and inflammation. Vasculitis, as we knew it, was mostly examined on the arterial side. Adams was one of a long line of researchers (starting with Rindfleisch) who saw the problem in MS on the venous side.
We now know that malfunctioning and injured endothelial cells (EC) is the first step in vasculitis, arterial and venous disease. What Adams found in autopsy brain tissue--fibrin deposition, thrombosis (small clots) and iron deposition--are all signs of endothelial breakdown. This leads to permeability of the blood brain barrier. Dr. Zamboni explained how this was like venous disease in other parts of the body in his Big Idea paper. He shows how altered venous hemodynamics begin this cascade---
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/
Today--because of the focus on Zamboni's discovery, this issue is being reexamined by neurologists. The obvious signs of venous disease confirmed by ultra high field MRI is too hard to deny. But instead of examining how this process is the same in the rest of the body, they are claiming that autoreactive t cells are damaging the BBB and endothelial cells.
The relationship between multiple sclerosis (MS) and the vasculature has been discussed in many facets: lesions centered by a small blood vessel are characteristically present in MS, as noted initially by Charcot1 on histologic analyses, and confirmed in vivo by very recent ultrahigh-field magnetic resonance imaging (MRI) studies.2 The disruption of small-vessel blood–brain barrier is a hallmark during the development of MS plaques. As an early event during the autoimmune cascade, autoreactive T lymphocytes migrate into the central nervous system and initiate a focal immune response. This inflammatory process can result in microvascular damage by different mechanisms: cytotoxic T cells may recognize antigens on endothelial cells and activate a clotting cascade which, in turn, leads to thrombosis.
http://www.nature.com/jcbfm/journal/vao ... 1396a.html
But the truth is---this cascade happens everywhere in the body without the need for cytotoxic t cells. (this was the genius of Dr. Zamboni's discovery.) It is only because the CNS is protected by the immune system that we see this secondary, not primary, reaction. And the larger question remains....what is causing the disruption of the blood brain barrier? Dr. Zamboni showed how edema, hypoxic injury, and a breakdown of the vessel wall due to endothelial stress creates this exact situation in venous disease in the body.
As far as restenosis--I still believe lifestyle, nutrition, exercise and endothelial health will help. Jeff's going on 4.5 years with no restenosis.
cheer
