Dr. Zamboni responds to the Harvard mouse study. He sees significance in the fact that the mice with ligated jugulars indeed developed hypoperfusion, which is present and otherwise unexplained in MS patients. He points out the limitation of the mice's lifespan. For an illness with the word chronic right in the name (Chronic Cerebrospinal Venous Insufficiency), the mice's lifespan is too short to allow for the chronic damage possible during the much longer human lifespan. CCSVI is suspected to be due to congenital abnormalities present at birth, and the most common age of MS diagnosis is at age 30 years, which is 60 times the duration of 6 months studied in these mice. And I am curious what Dr. Zamboni would think of the point that Dr. Sclafani made, that the dural sinuses in humans drain into the internal jugular veins but in mice the sinuses drain into the retroglenoid veins. IJVs are a more important conduit in humans than in mice.Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice
RESULTS INTERPRETATION
Posted by PaoloZamboni on 05 Apr 2012 at 10:16 GMT
This is a very nice article on animal model of MS and CCSVI. The experiment is well conduit and I would congratulate the Authors. The main problem lies in data interpretation. It seems to me that the main purpose is to "hide" a result on the one hand, and to just privilege a single negative on the other.
Let me explain better:
1) the “hidden result” is that only the group of rats with the ligated jugulars develops a problem of cerebral hypoperfusion. This aspect is not measured in both sham and EAE rats. This is a very important result because the cerebral hypoperfusion is a constant feature of human MS, clearly not explained by the autoimmune theory (1). Alternatively, it seems that hypoperfusion in the human being can be rather explained by the CCSVI (1-2). From this point of view the animal model confirms that the stenosis of the jugular veins leads to cerebral hypoperfusion, which is one of the aspects of human MS never reproduced in the animal model of MS. From this point of view this experiment is an important contribution in order to achieve a model similar to the human disease.
2) demyelination and neuro-degeneration occurs only in EAE animals, a fact long known, but in CCSVI or sham did not. Also clinical and neuro-inflammatory parameters were not responsive in CCSVI model. This is not surprising as 3-6 months of slightly reduced hypoperfusion are not likely to be able to determine a damage of this magnitude. It should be more interesting to assess more refined parameters at cellular and axonal level in CCSVI model respect to sham.
REFERENCES
1. D'haeseleer M, Cambron M, Vanopdenbosch L, De Keyser J. Vascular aspects of multiple sclerosis. Lancet Neurol. 2011 Jul;10(7):657-66
2. Zamboni P, Menegatti E, Weinstock-Guttman B, Dwyer MG, Schirda CV, Malagoni AM, Hojnacki D, Kennedy C, Carl E, Bergsland N, Magnano C, Bartolomei I, Salvi F, Zivadinov R. Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report. BMC Med. 2011 Mar 7;9:22.
No competing interests declared.
But what is meant by the more refined parameters at axonal and cellular level that could be studied in the CCSVI animal model? The finding that the ligated mice develop hypoperfusion could be compared to the sham and eae mice. Over a six months duration, what might be the effects that the hypoperfusion might have, on an axonal and cellular level, and how would they be measured?
