News today out of the University of Calgary from Dr. V. Wee Yong's team (Dr. Yong was the head of the panel of experts that served as medical advisory panel for the MS Society last year, advising the CIHR not to pursue clinical trials for CCSVI)  Dr. Yong's new research was funded by the Canadian Institutes of Health Research and the MS Society of Canada. (Could that be considered a conflict of interest?)

The reason I include a note regarding this study is because high levels of EMMPRIN are not unique to the MS brain lesions.  But first, let's cover what the Canadian researchers announced today.

http://www.physorg.com/news/2011-01-ms-canadian.html

Using a mouse model, researchers have discovered that a molecular switch called EMMPRIN plays an important role in MS. The researchers explored how in MS, EMMPRIN affects MMPs and the entry of leukocytes into the CNS to result in disease activity.

"In our studies we inhibited EMMPRIN and noticed a reduced intensity of MS-like symptoms in mice," says Dr. V. Wee Yong, a professor of Clinical Neurosciences at the Hotchkiss Brain Institute at the University of Calgary's Faculty of Medicine and the study's principal investigator. "Our data suggests that if we target EMMPRIN in patients with MS, we may reduce the injury to the brain and spinal cord caused by immune cells."

In addition to working with animal models, the authors also found that EMMPRIN is significantly elevated in the brain lesions of MS patients, indicating its potential significance in the disease.

"This study has identified a new factor in MS, the blockade of which resolves disease activity in an animal model of MS. The results are exciting as they offer new insights into the MS disease process", says Dr. Smriti Agrawal, a postdoctoral fellow in Dr. Yong's lab and the study's lead author.

"The authors have extended our knowledge of the molecules that regulate the trafficking of immune cells into the nervous system as occurs in multiple sclerosis. The current study identifies a new factor that can serve as a potential target of MS therapeutics," says Dr. Jack Antel, Professor of Neurology at McGill University.

(Medical definition for those who want to know more....EMMPRIN is Extracellular Matrix Metalloprotease Inducer.   EMMPRIN (also known as Basigin or CD147) is a multidomains, multifunctional glycoprotein located on the cell surface in physiological and pathological conditions including tumor cells.  EMMPRIN is associated with cell growth and adhesion, angiogenesis,  chaperone functions, immune cell activation, proMMP-1 activation, MMP induction and ECM degradation and remodeling)

But elevated EMMPRIN in the brain is not unique to MS.  Researchers have also noted that EMMPRIN is elevated in stroke and ischemic injury of brain tissue.

Elevated activities of matrix metalloproteinases (MMPs) following ischemic stroke have been shown to mediate ischemic injury as well as neurovascular remodeling. The extracellular MMP inducer (EMMPRIN) is a 58-kDa cell surface glycoprotein, which has been known to play a key regulatory role for MMP activities. The roles of EMMPRIN in stroke injury are not clearly understood. In this study, we investigated changes of EMMPRIN in a mouse model of permanent focal cerebral ischemia, and examined potential association between EMMPRIN and MMP-9 expression. Adult male CD-1 mice were subjected to permanent focal ischemia by intraluminal occlusion of the left middle cerebral artery (MCAO) under anesthesia. EMMPRIN expression was markedly upregulated in the periinfarct area at 2–7 days after ischemia compared to the contralateral non-ischemic hemisphere by Western blot analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals co-localized with vwF-positive endothelial cells and GFAP-positive peri-vascular astrocytes. In contrast, EMMPRIN signal did not co-localize with NeuN-positive neurons, or MPO-positive neutrophils. Dual fluorescent staining revealed that EMMPRIN co-localized with MMP-9. Our data also demonstrated that increased EMMPRIN expression correlated with increased MMP-9 levels in a temporal manner.

In summary, we report for the first time that EMMPRIN expression was significantly increased in a mouse model of permanent focal cerebral ischemia. The spatial and temporal association between increased EMMPRIN expression and elevated MMP-9 levels suggest that EMMPRIN may modulate MMP-9 activity, and participate in neurovascular remodeling after ischemic stroke.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375043/

 Here's another study on elevated EMMPRIN in ischemic brain injury--

Focal cerebral ischemia leads to the gradual disruption of the extracellular matrix. A key role in the turnover of the extracellular matrix is played by the system of matrix metalloproteinases (MMPs). In this study we describe changes of the MMP inducer protein (EMMPRIN) following experimental cerebral ischemia (induced for 3 h and followed by 24 h reperfusion, suture model) in rats. Extracellular EMMPRIN was measured by Western blot of the ischemic and nonischemic basal ganglia and cortex separately. Compared with the contralateral nonischemic area, the ischemic hemisphere showed a significant increase in EMMPRIN: basal ganglia, 158% +/- 4% (P < 0.05); cortex, 128% +/- 25% (P < 0.05). Immunohistochemistry was used to localize EMMPRIN on cerebral microvessels. EMMPRIN-positive microvascular structures were quantified by automatic morphometric video-imaging analysis and a significant increase in the number of cerebral microvessels staining positive for EMMPRIN in the ischemic basal ganglia was shown. The significant loss of microvascular basal lamina antigen collagen type IV in ischemic cortex and basal ganglia was calculated by Western blot. Measured by gelatin zymography, we demonstrated an MMP-2 and MMP-9 increase in the ischemic brain regions (P < 0.05). For the first time the MMP activation system EMMPRIN was shown to be relevant in cerebral ischemia. These results raise the possibility that the increased expression of EMMPRIN, the increase in MMPs and the damage of the basal lamina following cerebral ischemia are connected and part of a network of related changes.

http://www.ncbi.nlm.nih.gov/pubmed/16029217  

Two studies finding EMMPRIN elevated in brain tissue after an ischemic injury.  When will the MS researchers begin to consider ischemia as related to slowed perfusion and venous stenosis in CCSVI/MS and be done with EAE?   Perhaps new animal models will hasten that day.  We can only hope....

EDIT:  Found new research connecting EGCG (our friend, green tea--a natural iron chelator, anti-oxidant and anti-inflammatory) can down-regulate EMMPRIN--

EMMPRIN (extracellular matrix metalloproteinase inducer), a glycoprotein able to activate MMPs, were significantly reduced after 50 µg/ml EGCG treatment.

http://www.ncbi.nlm.nih.gov/pubmed/20446926

Another reason to take that EGCG supplement, or drink green tea. 

Joan