Research: Treating Reduced Blood Flow

Epub: D’haeseleer et al. Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1. Proc Natl Acad Sci U S A. 2013 Mar.

Background: Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown. 

Objective: We investigated whether the potent vasoconstrictor (contracts blood vessels) endothelin-1 (ET-1) is involved. 

Findings: We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein. The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on post-mortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to non-invasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. 

Conclusions: These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.

This week saw the leaking of the trial results of venoplasty to unblock veins. This current study suggests that the problem may not be with blocked veins of stuck valves but with the increased presence of endothelin-1, This is known to contract blood vessels, which would reduce blood flow through the veins. This may be made by cells in the brain and so is higher in blood vessels leaving the brain. The reduced blood flow effect found in MSers was inhibited using a blocker of endothelin-1 function called Bosentan, which blocks effect of endothelin-1 at the endothelin-A and B receptors. 

This looks like this could be CCSVI-2 on the way…ugh,  but be warned this drug can cause liver toxicity, aneamia, stops contraception working and can cause foetal harm and there is no evidence base to suggest that this results in any benefit. 

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Leave a Reply to Maren Rasmussen Cancel reply

  • There was some past research on endothelin-1 being elevated in MS:

    Stenosed blood vessels can also cause endothelin-1 to become elevated. The two are not exclusive, but would have a cumulative negative impact on cerebral blood flow. The abstract doesn't tell us whether or not the MSers felt better once their cerebral blood flow was normalized. Maybe we will see trials.

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