Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.
Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3535
cheerleader wrote:Fibrinogen was found to be the first invader to cross a broken blood brain barrier. It preceded demyelination, inflammation, and caused death of axons.
"Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation."
Just as Dr. Zamboni hypothesized in 2006 in his Big Idea paper, where he compared the MS process to that which he saw in chronic venous disease. Where fibrinogen initiated the degenerative process.
The FULL paper is online for free.
http://www.nature.com/ncomms/journal/v3 ... s2230.html
Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease.
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