One of the issues we have been hit with is how can MS be venous if inflammation suppression via revimmune metheylprednisolone etc helps people with MS.
I have offered that MS is an inflammatory disease and that is how we can account for the conundrum: the venous damage happens then the immune system responds to heal the damage and THAT causes damage of its own: inflammation itself hurts the brain.
I'd like to discuss research related to that line of thought here.
from CLiCK HERE
Thrombolysis heralded a new era of acute intervention for ischemic stroke, accompanied by an increasing need for comprehensive acute critical care support. There remains the prospect of novel cerebral protection strategies. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade, both in the CNS and in the periphery. Closely linked events are induction of a classic acute phase protein response, activation of the hypothalamic-pituitary-adrenal axis (HPAA) and sympathetic nervous system (SNS), and rise in body temperature, all of which appear to importantly influence the outcome. Thrombolysis aside, various therapeutic strategies have been trialed without success recently, primarily directed at influencing neuronal activity and survival directly. Inflammation itself offers an attractive target, mainly because of its potential to exacerbate the spread of damage to the ischemic penumbra. A promising novel therapeutic approach is the interleukin-1 receptor antagonist (IL-1ra), which limits the action of the cytokine IL-1, a pivotal mediator in the pathophysiology of acute neurodegeneration. We discuss inflammation and its mediators in acute ischemic stroke, the systemic stress, and acute phase protein responses to acute ischemic stroke, how inflammation is relevant in deteriorating ischemic stroke, the impact of physiological variables, and both current and emerging interventions for acute ischemic stroke.
This paper essentially says that in a stroke the inflammation itself expands the damage and makes it worse. They are going to try limiting the damage by stopping interleukin -1 with a drug.
This is very similar to the tysabri approach which blocks adhesion molecules and prevents inflammatory cells from going into the brain.
. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist
Again part of the damage is caused by inflammation and they are considering making some drugs similar to the ones we use in MS to help the situation.
Note I bolded the deal on "head injury". The mechanical damage caused by the CCSVI could be considered a type of head injury.
Ischemic stroke is the most frequent cause of persistent neurologic disability in modern Western societies. Albeit it is still not clear whether inflammation is merely an epiphenomenon or rather has a disease-promoting function, accumulating evidence implicates inflammation in many forms of acute neurodegenerative disorders including ischemia. The immune cell influx during a neuropathological event is thought to be elicited by glial cells, especially microglia.This article reviews the cellular and molecular pathways involved in stroke-induced inflammatory response in the CNS. We focused on how CNS innate immune cells including microglia and macrophages play integral roles in receiving and propagating inflammatory signals, and how activated microglia secrete a wide range of factors. We present the relevance of the expression of adhesion molecules after ischemia including selectin, immunoglobulin superfamily, integrins, and the role of inflammatory mediators such as cytokines, chemokines and matrix metalloproteinases. Further, we explore the role of transcription factors in inflammation, and the function of immunomodulation and innate and adaptive immunity in brain ischemia, focusing on immunosupression therapies for acute stroke. Although several approaches for anti-inflammatory treatment have proven effective in animal models, clinical trials of immune system modulation therapy after stroke have not yet proved successful. There is still much to be done in order to translate interesting findings into therapies, but undoubtedly studying the cellular and molecular pathways may not only improve our understanding of inflammatory mechanism but also serve as a basis for designing effective therapies.
Again they are using immunosuppression for stroke to limit the damage after the stroke.
No one argues that a stroke is "autoimmune", yet the same types of drugs that help MS also help stroke victims reduce the level of damage.
The fact is that damage in the brain is always accompanied by damaging inflammtion. This is true in spinal cord injury too: inflammation causes some of the damage and strategies that limit it will help limit the secondary damage to the area after the SCI has occurred.
I will add that much earlier in the big thread we explored the research related to inflammation in venous ulcer, the prototypical model for the CCSVI caused MS lesion. Just like in stroke, much of the damage in a venous ulcer comes from inflammation secondary to the venous insufficiency.
Thus we see why it is not true that "if (insert any immune suppressive drug here) helps, that proves MS has to be autoimmune."
If MS lesions are caused by CCSVI then inflammation is going to be part of the process and it is going to be damaging to the tissue. And just like in stroke, suppression will help limit it somewhat. But the cure is to take away the cause of the injury, not just to take away the inflammation.
Ok we can talk about it if we like! Add some other papers to develop this!