CCSVI treatment is worthy even if not causal for MS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

CCSVI treatment is worthy even if not causal for MS

Postby frodo » Wed Dec 11, 2013 2:09 pm

CCSVI treatment is worthy for patients with depression even if not the cause for MS. It has been shown that endothelial weakness can cause depresion. This article is taken from the Jounal of Neuroinflammation and it looks like writen by neurologists.

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence.


About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer's disease.

In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD.

More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard.

Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches.
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Re: CCSVI treatment is worthy even if not causal for MS

Postby Cece » Wed Dec 11, 2013 2:38 pm

That is interesting. Might lead to new pharmaceuticals for depressive disorder that address the oxidative stress and the neuroinflammation, and it begins to explain why diet and exercise can work as treatments against depression. I think the understanding of nitric oxide's role in the endothelium is relatively new.

It's not proven that CCSVI treatment improves neurovascular unit dysfunction but it seems likely.
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Re: CCSVI treatment is worthy even if not causal for MS

Postby Rogan » Sun Mar 02, 2014 1:19 pm

This summary paper of the "Neurovascular Unit" has been posted on Facebook….

It is very thick and interesting…

Some of the quotes from this link

Estimations suggest that the human brain contains up to 100 billion vessels, i.e., a vessel for each neuron. The vascular system developed more recently in evolution than the nervous system.

Indeed, by releasing ‘‘angiocrine’’ factors, endothelial cells (ECs) not only produce instructive signals for neural development, but also support normal functioning, ensure maintenance, and promote reparative regeneration of the CNS (Butler et al., 2010).

This ‘‘neurovascular unit’’ is only one of the examples of the intertwined connection between the neural and vascular system.

The endothelium is supported by a basement membrane and enwrapped by pericytes, astrocytic endfeet, and neuronal synapses, all together establishing the neurovascular unit.

and an explanation of why proper blood flow matter to the endothelial…

CBF (cerebral blood flow) control occurs in various neurological diseases and can contribute to neuronal damage via neurovascular uncoupling and hypoperfusion (Iadecola, 2004). Oxidative stress in ECs (endothelial cells) seems to be a common cause of perturbed functional hyperemia and cerebrovascular autoregulation in Alzheimer’s disease (AD), arterial hypertension, and diabetes mellitus by interfering with endothelial production of vasodilatory substances

and a possible pharma solution in the future…..

At the molecular level, dysregulated PDGFRb signaling is one of the few pathways, discovered so far to cause functional BBB maintenance defects evoking secondary neurological dysfunction. Indeed, disruption of this EC/pericyte molecular communication causes progressive pericyte loss and coincident BBB hyperpermeability after birth (Armulik et al., 2010; Bell et al., 2010). However, as these mutant lines lack pericytes already in development, it is unclear to what extent loss of pericytes in adulthood can contribute to BBB leakage; inducible gene inactivation studies in pericytes will be required to answer this question. Structural junctional abnormalities, increased transendothelial transport and basal lamina deficits, thought to impair anchoring of astrocytic endfeet to the vessel wall, are believed to cause the BBB dysfunction in pericyte-deficient mice (Armulik et al., 2010; Bell et al., 2010).

and more evidence…

Also noteworthy, vascular dysfunc- tion is present early in neurodegenerative diseases, even prior
to onset of neuronal death (Garbuzova-Davis et al., 2011; Iadecola, 2010), implying that vascular abnormalities actively contribute to neurodegeneration.

and their testing on ALS animals

From the above, it is evident that angiogenesis offers a range of therapeutic opportunities. Given the scope of the review, we will outline, as prototypic example, one emerging neurovascular therapeutic approach, which has recently progressed to clinical testing.

The clearest example of a therapeutic candidate for neurodegeneration is VEGF.

The benefit of ICV delivery of VEGF protein for ALS patients is currently being clinically evaluated in phase I/II trials.

to finally their hope for future therapies

For instance, emerging evidence suggests that vessel growth in the brain relies in part on specific, perhaps even unique proangiogenic signals. Identifying their molecular nature offers great promise to understand neurovascular disorders and to develop novel neurovascular medicine. Second, the role of pericytes has turned out to be more important than previously recognized. Do pericyte abnormalities causally contribute to neurodegeneration and other types of neurological disorders, and can they be therapeutically targeted? Finally, the brain vasculature is now considered to be a major contributor of the neurogenic stem cell niche. Can this process be exploited for brain repair? Finding an answer to these and other questions promises to be a scientifically exciting journey with great translational potential.
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