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Cell culture work showed that lack of iron reduces the ability of microglia to express cytokines (TNF-α and IL-1β) involved in remyelination

Cece wrote:http://www.springerlink.com/content/phpvyh4yfhv1q4f5/

DIAGNOSTIC NEURORADIOLOGY
The anatomy of collateral venous flow from the brain and its value in aetiological interpretation of intracranial pathology
J. Andeweg
Abstract
For more than a century, available data concerning collateral venous outflow from the brain have received insufficient attention, as existing theories did not assign practical importance to them. Ideas concerning arterial blood supply and circulation of cerebrospinal fluid were considered more relevant. But available data afford a schematic model of cerebral venous outflow that does have important pathophysiological consequences. Principal outflow through the internal jugular veins can be substituted completely by the large vertebral plexuses, through communications at the cranial base. Emissary veins of the skull vault are small and few in number. Outflow from the deep venous system through the great vein of Galen can be substituted by choroidal, thalamic and striate anastomoses toward the basal vein. So-called intracerebral venous anastomoses through the centrum semiovale towards the convexity are nonexistent or negligible. Instead, a venous watershed exists separating paraventricular white matter from a layer of subcortical white matter. In most infants, the cavernous sinus is not yet connected to the cerebral veins. Once such communications have been formed, important collateral pathways exist through basal and Sylvian veins via the cavernous sinus to the pterygoid plexuses. Simultaneous hindrance of principal and collateral venous outflow will lead to elevated venous pressure and eventual insufficiency of cerebral blood flow (CBF). This will cause increased intracranial pressure, and ventricular enlargement due to periventricular atrophy. The slow phase of the two-compartment model of CBF coincides with the paraventricular white matter area of the deep venous system. In the neonate CBF was found to be still very low, and in the two compartments CBF increases at a different rate to a maximum in childhood. In hydrocephalus, measurement of CBF in the slow deep compartment, rather than the fast cortical one, will be most informative.

The slow phase of the two-compartment model of cerebral blood flow coincides with the paraventricular white matter area of the deep venous system.
Periventricular white matter lesions are especially common in MS.
If even in a healthy person, flow is slow through this section of the brain, then damage due to unnaturally slowed flow due to outflow obstructions could be expected to accumulate here.

Bethr wrote:...........It seems the majority of PWMS have low iron. Or is it just unavailable, ie: a fault in ferroportin?
Genmati from memory found a high number of FPN genes in more advanced MS.
I really need to go back and read his papers from IVSND again I think.

1eye wrote:What evidence is there for saying the majority of "MS" patients have low iron?

I have heard of a few people on this forum having regular phlebotomy because it make their "MS" feel better. If anything, that would come from the initial condition being an overload of iron.

The exact underlying mechanism by which brain iron accumulates in MS is not fully understood. Iron transport across the blood-brain barrier is dependent on iron transport proteins, predominantly by transferring receptors expressed on brain epithelial cells [59]. Other transporters may also facilitate iron transport across the blood-brain barrier, such as the divalent metal transporter (DMT) and the lactoferrin receptor [60]. It is also not yet clear if increased brain iron deposition is implicated in MS pathology or merely reflects an epiphenomenon [3, 61]

BethR wrote:Across the general population the majority of women have low iron levels, so to me that state is normal, MS or not. MS predominantly affects women.

1eye wrote:BethR:

From the reference you gave:

The exact underlying mechanism by which brain iron accumulates in MS is not fully understood. Iron transport across the blood-brain barrier is dependent on iron transport proteins, predominantly by transferring receptors expressed on brain epithelial cells [59]. Other transporters may also facilitate iron transport across the blood-brain barrier, such as the divalent metal transporter (DMT) and the lactoferrin receptor [60]. It is also not yet clear if increased brain iron deposition is implicated in MS pathology or merely reflects an epiphenomenon [3, 61]

I think it may be more fully understood than it used to be. Dr. Zamboni, possibly others, called it extravasation. This sounds to me like actual leakage of venous blood cells (with a very low level of oxygen due to it being around the brain long enough to have gotten all reduced to more elemental iron) across a pathologically permeable blood brain barrier. When these die they leave iron behind. I don't think it's an epiphenomenon.