NEW: research in Brain-Oxidative damage in MS lesions

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

NEW: research in Brain-Oxidative damage in MS lesions

Postby cheerleader » Sat Jun 11, 2011 9:31 pm

Full paper is available for free from Brain. Highly recommended-
More from Dr. Lassman and his team in Vienna.

link

In contrast to these previous studies, we show here that DNA and lipid oxidation is associated with ongoing demyelination and neurodegeneration in active multiple sclerosis lesions. Furthermore, we show for the first time that acute cell injury and cell death of oligodendrocytes, axons and neurons in multiple sclerosis is linked to profound cytoplasmic and nuclear oxidative damage. The reason for the different results between our current and previous studies is not entirely clear. The most likely explanation comes from our observation that oxidized DNA and lipids were mainly present in a small zone of active multiple sclerosis lesions, which represents that previously described as the area of initial demyelination (Marik et al., 2007) or the ‘prephagocytic’ lesion (Barnett and Prineas, 2004; Henderson et al., 2009). Such lesions or lesion areas may not have been included in earlier studies. It has been shown previously that oxidized phospholipids and MDA epitopes are present in apoptotic cells as well as in apoptotic bodies ingested by macrophages (Chang et al., 1999). Apoptotic oligodendrocytes are predominantly seen in multiple sclerosis lesions in areas of initial (prephagocytic) demyelination (Barnett and Prineas, 2004; Marik et al., 2007). Furthermore, apoptotic cell death through oxidative mechanisms may exert proinflammatory and immunogenic actions (Chang et al., 2004), which in part may explain the progressive increase in inflammation with lesion maturation in multiple sclerosis (Marik et al., 2007; Henderson et al., 2009).


In summary, our study provides evidence for an important role of oxidative damage in the pathogenesis of demyelination and neurodegeneration in multiple sclerosis lesions, which may act in addition to, or in cooperation with nitric oxide radicals, as described previously (Bagasra et al., 1995; Zeis et al., 2009). It further shows—for the first time—that the analysis of oxidized lipid epitopes in multiple sclerosis lesions allows identification of acute damage of oligodendrocytes, axons and neurons at different stages of lesion formation. Our data also suggest that oxidative damage is in part related to inflammation, that it affects different cellular components of the CNS, but that myelin, oligodendrocytes, neurons and axons may be more sensitive to oxidative damage than astrocytes.


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Postby questor » Sun Jun 12, 2011 10:06 am

This appears to suggest the importance of finding and using antioxidants to help clean-up and prevent the damage of free-radicals produced by oxidative stress.

A quick glance at wikipedia's free article on oxidative stress shows this (keep in mind that you generally get what you pay for):

Wikipedia Article on Oxidative Stress wrote:The use of antioxidants to prevent disease is controversial. In a high-risk group like smokers, high doses of beta carotene increased the rate of lung cancer.[18] In less high-risk groups, the use of vitamin E appears to reduce the risk of heart disease.[19] In other diseases, such as Alzheimer's, the evidence on vitamin E supplementation is mixed.[20][21] Since dietary sources contain a wider range of carotenoids and vitamin E tocopherols and tocotrienols from whole foods, ex post facto epidemiological studies can have differing conclusions than artificial experiments using isolated compounds. However, AstraZeneca's radical scavenging nitrone drug NXY-059 shows some efficacy in the treatment of stroke.[22]
Oxidative stress (as formulated in Harman's free radical theory of aging) is also thought to contribute to the aging process. While there is good evidence to support this idea in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[23][24] recent evidence from Michael Ristow's laboratory suggests that oxidative stress may also promote life expectancy of Caenorhabditis elegans by inducing a secondary response to initially increased levels of reactive oxygen species.[25] This process was previously named mitohormesis or mitochondrial hormesis on a purely hypothetical basis.[26] The situation in mammals is even less clear.[27][28][29] Recent epidemiological findings support the process of mitohormesis, and even suggest that antioxidants may increase disease prevalence in humans (although the results were influenced by studies on smokers).[30]

I'm supplementing these days with alpha lipoic acid, SAME, acetyl l-cysteine, and Vitamine E in addition to several anti-inflammatories (like bromelain).

Hopefully, these help to reduce the damage and apoptosis that can result from oxidative stress.

Here's a link to a BodyEcology site that lists ways to fight and prevent oxidative stress (another free article, and they may try to sell you something, but interesting...):

Preventing Oxidative Stress

They list "too much sugar" as contributing to oxidative stress, I also find refined sugar to be pro-inflammatory and have put it in my "best to avoid" category.

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Postby Bethr » Sun Jun 12, 2011 10:40 am

Douglas Kell has some excellent work out on this. he's trying to bring all the different research together, hence you'll see in the full text he has referred to over 2000 studies (including Zamboni).

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

The abstract is here, the full text is available here also (click through top right).
http://www.biomedcentral.com/1755-8794/2/2/abstract

I found this fascinating, especially how some anti-oxidants become pro-oxidants under some conditions. The catalyst is iron behaving badly.

a full PDF available here http://www.biomedcentral.com/content/pdf/1755-8794-2-2.pdf
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Postby questor » Sun Jun 12, 2011 11:15 am

A list of antioxidants found to be useful in treating oxidative stress (in Alzheimer's Disease, in this case).

http://www.ncbi.nlm.nih.gov/pubmed/21605052 wrote:Abstract:

Alzheimer's disease (AD) brain is characterized by amyloid β-peptide (Aβ) deposits, neurofibrillary tangles, synapse loss, and extensive oxidative stress. Aβ-induced oxidative stress is indexed by protein oxidation, lipid peroxidation, free radical formation, DNA oxidation and neuronal cell death. Oxidative stress is combated by antioxidants. Antioxidants and nutrition have long been considered as an approach to slow down AD progression. In this review, we focus on antioxidants that have been shown to protect against Aβ-induced oxidative stress, particularly vitamin E, ferulic acid, various polyphenols, including quercetin and resveratrol, α-lipoic acid, N-acetyl-L-cysteine (NAC), curcumin, epigallocatechin gallate (EGCG), and γ-glutamylcysteine ethyl ester (GCEE). Brain-accessible antioxidants with both radical scavenging properties and ability to induce protective genes are hypothesized to be helpful in treatment for AD.


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Postby ikulo » Sun Jun 12, 2011 11:37 am

Great posts. I learn something new every day at TiMS. I'd like to add to this info with a link to the Linus Pauling Institute. They have gathered information/studies on various foods and nutrients. http://lpi.oregonstate.edu/infocenter/ (click through on the left side)

Some nutrients aren't absorbed well by the body and some should be taken with other nutrients/at certain times/etc..., so before you go out and spend money on supplements I recommend reading the website.
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Postby cheerleader » Mon Jun 13, 2011 8:56 am

This form of oxidative damage to the brain is exactly what happens in situations of hypoxic stress. If CCSVI is truly creating the lesions and damage to the brain, this is what it would look like. Lassman's study has provided another link to how slowed perfusion and low O2 could manifest damage.

Here's a study on how hypoxic stress looks in rodent brains....

High altitude exposure results in decreased partial pressure of oxygen and an increased formation of reactive oxygen and nitrogen species (RONS), which causes oxidative damage to lipids, proteins and DNA.

(Note that this is almost exactly what the researchers found in the MS brain tissue due to oxidative damage)

Exposure to high altitude appears to decrease the activity and effectiveness of antioxidant enzyme system. The antioxidant system is less in brain tissue and is very much susceptible to hypoxic stress. The aim of the present study was to investigate the time dependent and region specific changes in cortex, hippocampus and striatum on oxidative stress markers on chronic exposure to hypobaric hypoxia. The rats were exposed to simulated high altitude equivalent to 6100 m in animal decompression chamber for 3 and 7 days. Results indicate an increase in oxidative stress as seen by increase in free radical production, nitric oxide level, lipid peroxidation and lactate dehydrogenase levels. The magnitude of increase in oxidative stress was more in 7 days exposure group as compared to 3 days exposure group. The antioxidant defence system such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) levels were significantly decreased in all the three regions. The observation suggests that the hippocampus is more susceptible to hypoxia than the cortex and striatum. It may be concluded that hypoxia differentially affects the antioxidant status in the cortex, hippocampus and striatum.


http://www.ncbi.nlm.nih.gov/pubmed/16911847

the endothelial health program was created with anti-oxidant healing and NO balancing in mind. EGCG, alpha lipoic acid, bromelain, quercetin and other supplements that can cross the blood brain barrier.

Our bodies constantly react with oxygen as we breathe and as our cells produce energy. However, our use of oxygen is a double-edged sword: we need oxygen to survive, but as a consequence of using oxygen, highly reactive molecules, known as “free radicals,” are produced. Free radicals are atoms or molecules with electrons which have lost their partner electron, often as a result of our respiratory or metabolic process, or from outside influences. Free radicals can disrupt the balance of NO, damage the endothelium and leave it overly permeable, allowing toxins to pass into our tissues9. In most instances, our body has an adequate supply of antioxidants obtained from food to neutralize these free radicals, but if the body is depleted, or if there are too many coexistent factors, injury to the endothelium and a change in the balance of NO may occur.

http://www.ccsvi.org/index.php/helping- ... ial-health

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Postby jgalt2009 » Tue Jun 14, 2011 6:34 pm

Just a brain-storm... wouldn't it be better to be slightly anemic than hyperactively producing MMPs? Periodic clinical exsanguination perhaps? Lower Fe = lower O2 radicals?
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Postby cheerleader » Wed Jun 15, 2011 8:26 am

jgalt2009 wrote:Just a brain-storm... wouldn't it be better to be slightly anemic than hyperactively producing MMPs? Periodic clinical exsanguination perhaps? Lower Fe = lower O2 radicals?


Hi jgalt--I've spoken with Dr. Haacke about this (an inventor of SWI technology, which measures iron content in the brain) and his comment is that it isn't about the iron content in the blood, or even the blood itself...it's the fact that plasmic particles are able to cross the blood brain barrier and there is cellular death. This alone is enough to create iron release and oxidative damage, even if the patient is iron deficient. Also, pernicious anemia and vit. B12 deficiency are often misdiagnosed as MS. I'm not sold on the idea of blood letting....but many on this forum are, and get relief from this.

Here's an interesting study on iron dysregulation in MS:
http://www.ncbi.nlm.nih.gov/pubmed/18408021
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Postby Bethr » Wed Jun 15, 2011 1:14 pm

I wouldn't recommend the bloodletting method to most, as I believe the only reason it worked for me is because I have a C282Y gene that increases my iron absorption and I already had a mild iron overload and high transferin saturation before I developed the brain lesion. I think the iron problems relate more to storage of iron which need not be in ferritin.
Once absorbed iron cannot be excreted from the body, but stays in storage, and will not necessarily show up in a blood test as it collects in organs. Especially in the presence of pathogens, iron is hidden away by the body as part of the immune response, so it is unavailable for growth of cancers and viruses etc, and is not available for the bodies daily needs.
Patient may test as anaemic even when storage in organs is high.

Douglas Kell is researching whether anti-oxidants together with chelation would address the reduction of iron/metals stored in the body.

People with classic iron overload often have initial symptoms of brain fog and fatigue, especially women, which is reversed when iron loads are reduced. We can often tell when we need another phlebotomy as the symptoms return.
That's what I experieinced, and it has now reversed.
No further brain problems.
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