We've been discussing how Lyme bacteria and the JC virus can harm and destroy brain tissue....but what allows these infectious agents into brain tissue in the first place?  Marie brought this very important point up in the discussion thread.   If the blood brain barrier were functioning correctly, these agents would not be an issue.  They just wouldn't be able to harm the brain.

The Blood Brain Barrier (BBB) is very important in keeping circulating blood out of brain tissue.  

The common wisdom is that in MS, the BBB is being breached in some mysterious fashion by T-cells that are punching thru and randomly attacking myelin in the MS brain. 

Current definition:

The blood-brain barrier is the semipermeable layer of cells within the capillaries of the central nervous system. When functioning normally, the blood-brain barrier prevents foreign invaders (such as viruses) and immune cells from passing out of the bloodstream and into the central nervous system. It also allows oxygen and essential nutrients to enter the central nervous system.

In multiple sclerosis, immune cells are allowed to enter the central nervous system, implying that the blood-brain barrier is damaged or compromised in some way. These immune cells, called T lyphocytes, attack the myelin in the brain and spinal cord, causing the lesions which lead to MS symptoms.

http://ms.about.com/od/glossary/g/blood_brain.htm 

But what if those t-cells are being invited to cross over due to an already breeched BBB?  What if it is CCSVI creating a break in this barrier?  We already have a known model for how this happens.....

Here is a wonderful hypothesis paper on how raised venous pressure affects the tight junctions of the endothelium and allows a break in the BBB.   It was written in 2007, before Dr. Zamboni published his research on the extracranial venous blockages he found in CCSVI,  and was inspired by the work of Dr. Schelling.  It uses the example of how dural arteriovenous fistulas (DAVFs) block veins and increase venous pressure, causing tight junctions to separate and t-cells to slip through and create myelopathy.  Just like MS.....

So, is the break in the BBB caused by some mysterious event where t-cells suddenly punch through and attack myelin  OR  could the break in the BBB be caused by raised venous pressure and an opening up of the tight junctions---just like it is in a dural arteriovenous fistula???

Once again, Ockham's Razor comes to mind....

I recommend reading the complete paper for a full understanding of the hypothesis.  Here's the link:

http://www.direct-ms.org/sites/default/files/Talbert%20Venous%20pressure%20MS%2008.pdf

Here's a bit of the paper to get you interested....

Raised venous pressure as a factor in multiple sclerosis

David G. Talbert *

Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Du Cane Road,

London W12 ONN, United Kingdom

Received 22 September 2007; accepted 6 October 2007

Summary-- It is hypothesised that the inflammatory condition seen in MS and the progressive myelopathy that is being successfully halted by obliteration of dural arteriovenous fistulas (DAVFs), may actually be two sides of the same coin.

Excessive venous hypertension can stretch vein walls sufficiently to separate the tight junctions between endothelial cells forming the blood-brain-barrier (BBB). Colloids, etc., but not necessarily erythrocytes, could then pass through the exposed porous basement membranes. The resulting changes in osmotic pressure, etc. would disrupt the axon and dendrite internal transport systems, leading to their disintegration. The normal inflammatory processes which would follow, might be indistinguishable from those associated with autoimmune disease.

Ascending progressive myelopathy and disablement are associated with an intracranial DAVF when its outflow enters the spinal venous system and descends past the cervical region. This can be arrested, and some degree of recovery produced, if the DAVF can be successfully eliminated or blocked. However, if the DAVF outflow is entirely into the spine, intracranial venous pressure may be normal and so there is nothing to alert the clinician to the presence of an intracranial DAVF.

It is suggested that where spinal MS has been diagnosed from clinical observations, patients should be referred for angiological investigation to search for DAVFs within the head to identify any treatable subjects.

c 2007 Elsevier Ltd. All rights reserved.

Introduction

MS relation to veins

Multiple sclerosis (MS) is characterized by multiple plaques of demyelination within the brain and/or

spinal cord, currently attributed to an autoimmune process, following some as yet unidentified event.

Close relatives have increased chance of developing MS, but no known links exist between MS and any

infection [1]. Early investigators noted that plaques formation was not completely random. In the spine

there appeared to be an underlying segmental pattern. Plaques in the CNS generally appear to be related

to veins. Tan et al. [2] studied 95 brain MS lesions using magnetic resonance imaging (MRI) techniques in vivo. They found a central vein was visible in all but one. The lesions typically had a basically ovoid shape whose long axis correlated well with the course of the vein, whereas using the same technique on cases of hypoxic ischemic  white matter, lesions bore no relationship to venous patterns. Kidd et al. [3]  found large cortical lesions, which pass around gyri, were likely to reflect involvement of the central vein of the gyrus.

Sources of spinal venous hypertension

 Retinopathy and optic nerve pathology are frequent early clinical signs of MS but also occur with acute raised intrathoracic pressure as blood is forced back into the head producing surges of intracranial venous pressure (‘Valsalva retinopathy’) [4–13] . Apart from such acute events, chronic venous hypertension may result from arteriovenous anastomoses (AVA), in particular dural arteriovenous fistulas (DAVFs), within the head [14,15]  or spine [16] . Borden et al. [17]  recognised the various pathological significances of the drainage paths of intracranial dural arteriovenous fistulas (DAVFs). They suggested three categories; type I draining entirely within the skull, type III draining entirely into the spinal venous system, and type II with mixed drainage. Using in vivo magnetic resonance imaging (MRI), Kwon et al. [18]  observed that distension of ophthalmic veins occurs in grade II but not in grade III. In contrast spinal dilated leptomeningeal or medullary vessels were not seen in grade I, but were in 100% of grade III cases. Cognard et al. [15]  found that in cases where drainage was purely spinal, progressive myelopathy occurred in 50% of cases. Brunereau et al. [14]  compared two such spinal drainage groups and found that where grade III drainage could be traced to the lumbar region it was clinically associated with slowly progressing ascending myelopathy involving first the lower and then the upper limbs. On the other hand, where drainage could only be traced as far as the cervical region of the cord, myelopathy did not seem to occur. Fistulas associated with myelopathy also occur in the spinal vasculature, where they may be recognised by the occurrence of reversed or severely reduced local spinal vein flows.

The strong clinical links between disability and factors producing CNS venous hypertension, raises the

possibility that the unknown initial event [1]  might be mechanical.

Hypothesis

 That the initial event in one form of MS is endothelial cell tight junction separation due to radial distension of veins in the head and/or spine by excessively raised transmural pressures. Overt failure of the vein wall may not occur, but separation of endothelial tight junctions would result in local breaching of the blood-brain-barrier (BBB). The resulting changes in osmotic pressure, pH, Na/K balance etc. would then disable the intra-axon and intra-dendritic transport systems, on which these cell extensions depend for normal function, leading to their degeneration. This in turn would trigger an intensive but completely normal inflammatory scavenging reaction, secondary to the primary damage caused by disruption of the BBB.

Hence, anti-inflammatory treatments would have no effect on the incidence of this form of MS. Arteriovenous anastomoses of various kinds, or venous obstruction would provide the underlying chronic

venous hypertension.