that contributing to MS

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

Postby LR1234 » Mon Mar 14, 2011 9:10 am

Last edited by LR1234 on Tue Mar 06, 2012 1:14 am, edited 3 times in total.
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Postby cheerleader » Mon Mar 14, 2011 9:17 am

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Hi North--just checked out your thread. Good stuff! I believe the fibrin is most-likely a result of diffuse cerebral hypoxia. It was the hypoxia induced coagulation cascade that I looked into after Jeff's diagnosis in '07 with MS. He came home from a week at high altitude with 20 lesions, 6 enhancing, and the strangest blood numbers. High SED, hypercoagulation, high liver enzymes and jaundice and petechiae. His neuro said it wasn't related to MS, but that got me on the vascular trail...and researching endothelial dysfunction and how to over come it.

Here's the paper that cinched it for me--you'll see how fibrin fits into the picture--

Cerebral Ischemia-Hypoxia Induces Intravascular Coagulation and Autophagy.

F Adhami, G Liao, YM Morozov, A Schloemer, VJ Schmithorst, JN Lorenz, RS Dunn, CV Vorhees, M Wills-Karp, JL Degen, RJ Davis, N Mizushima, P Rakic, BJ Dardzinski, SK Holland, FR Sharp, CY Kuan

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.

Here's more on fibrin---

One of the most surprising findings of the present study is that the decline of CBF in conjunction with hypoxia is sufficient to induce rapid microvascular thrombosis and fibrin deposition within the brain (Figure 9) . By analyzing challenged fibrinogen-null mice we have established that fibrin(ogen) plays an important role the reperfusion deficits and brain infarction (Figure 10) . These results suggest that if cerebral ischemia is accompanied with hypoxia, this combination can precipitate local coagulation and impede reperfusion after ischemia, similar to the previously described no-reflow phenomenon after cerebral ischemia5 and cardiac arrest.56 It seems likely that fibrin stabilization of platelet thrombi is a major determinant of brain tissue damage. If so, we would predict that a similar, if not more impressive, protection from tissue damage could be realized in mice with a profound defect in platelet function. It is also conceivable that fibrin-mediated inflammatory processes drive secondary tissue damage in the brain. Thus, the modified Levine/Vannucci model described here may be useful for testing new therapies to restore postischemic reperfusion in the face of thrombolytic agents and other approaches to reopened large vessels.

Regarding the mechanism of ischemia/hypoxia-induced thrombosis, it seems likely that hypoxia alters the balance between anti- and procoagulation properties of the endothelial cells in cerebral blood vessels. Although focal ischemia can trigger platelet accumulation and fibrin deposition, these events typically show a late-onset after a transient hyperemia phase.49,53 In contrast, the present study shows that the combination of ischemia and hypoxia precipitates these events almost immediately. Understanding the mechanism by which combined ischemia-hypoxia alters the homeostatic properties of endothelial cells in cerebral vessels may suggest novel prophylactic therapies in clinical situations when the imminent risk of cerebral ischemia and hypoxia is high, such as coronary bypass surgery.

Here's the whole paper...enjoy-
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
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