More about pattern III

[frodo]

Pattern III in MS lesions is a specific kind of demyelination that looks hypoxic, and therefore it could be more related than others to CCSVI. Pattern III is known as "distal oligodendrogliopathy" because oligodendrocytes die in that specific way.

A previous text (available at http://www.ajnr.org/content/27/5/954.full) used to say that lesions are similar to the early stages of WM ischemia and may therefore reflect hypoxic WM damage. A pathologic process similar to ischemia could be induced in inflammatory conditions by 2 mechanisms: vascular impairment leading to defective microcirculation or local production of toxins that alter the mithocondrial energy metabolism.

Now there is a new publication abouts it. The main conclusion is that under metabolic stress conditions similar to CCSVI, oligodendrocytes show significant reduction in glycolytic ATP production that is required for myelin maintenance.



Oligodendrogliopathy in Multiple Sclerosis: Relation to Low Glycolytic Metabolic Rate of Oligodendrocytes

http://www.neurology.org/content/86/16_ ... .004.short

Objective: To determine the relationship between the bio-energetic properties of oligodendocytes (OLs) and their response to metabolic stresses that mimic the multiple sclerosis (MS) lesion micro-environment.

Background: The production of myelin by OLs is a highly energetic process, requiring mitochondrial oxidative phosphorylation (OXPHOS) for ATP production and glycolysis/lactate to provide the carbon backbones necessary for lipid biosynthesis. Oligodendrogliopathy, which features the dying back of oligodendrocyte terminal processes, is a distinct type of injury response observed in MS lesions. This dying back process in MS has been linked to metabolic stress, which in MS lesions reflect disturbed micro-circulation with associated ischemia and/or production of toxic metabolites that disturb mitochondrial energy metabolism (Lassmann 2003).

Methods: We used OLs isolated from adult human brain specimens to examine their injury responses (survival, process extension) to reduced trophic factor, low glucose, and hypoxia conditions as a model of oligodendrogliopathy observed in MS lesions. We further examined the underlying bio-energetic properties of OLs using a Seahorse XF96 extracellular flux analyzer under the basal, metabolic stress and recovery conditions. Results: Human OLs grown under the above stress conditions for 48 hours showed only a marginal increase in [percnt] of TUNEL+ cells but a significant decrease in process area per cell. Basal aerobic glycolysis under optimal conditions provides the majority of ATP production in OLs. Under stress conditions, this ATP production is significantly decreased. Removal of stress conditions for 48 hours allowed for recovery of ATP production that occurred under the metabolic stress conditions.

Conclusions: Oligodendrocytes under metabolic stress conditions show significant reduction in glycolytic ATP production that is required for myelin maintenance. Here we show that the restoration of optimal metabolic conditions can restore energy production in human OLs. It remains to be determined when such intervention will result in long-term cell survival.

[Rogan]

"In MS has been linked to Metabolic Stress"

Fascinating article.

What factors besides fluid flow could possibly contribute to this stress?

Found in a specific part of the body?


What causes Metabolic Stress?