A Disaccharide which may help in SCI related inflammation.

Loading of the spinal fluid with binding capable , “less than the whole” segments of a matrix protein which blocks axonal regeneration may be helpful in stopping the action of proteoglycans which have become loose canons, leading to uncecessary inflammation..

It is interesting that we always assume the body is so constructed that there is a way to fix anything. We just have to figure out how to do it, which herb of the earth cures it etc. The odd thing is that this always turns out to be true.

In this article we deal with a structural protein, a polymer, just like the fibers that make up your carpet are polymers, which just so happens to have big implications in the immune system, if anything goes wrong. The complexity of the body is sometimes flat out unbelievable; yet, its inherent fixability is also a miracle.

Proteoglycans have always been a hot subject. They still are today.
Podichetty in Cell Mol Biol (Noisy-le-grand). 2007 May 30;53(5):4-18, from the Cleveland clinic, discusses many inflammatory chemicals felt to be associated with disc degeneration. The intervertebral disc, which is made up of a collagenous annulus outside and a softer pulposus inside (sort of like the gel pad in a running shoe), Podicehtty suggests that while the pulposus has active metabolism to make proteoglycans, the annulus has less of this. See also Seguin Matrix Biol. 2006 Sep;25(7):409-18. 2006 Aug 23, which shows a role for p38 MAPK, NF Kappa B, and ERK in depletion of aggregan/proteoglycans.

From an equally distinguished institution is an author which says, by comparison, that BOTH the annulus outside and the pulposus inside make lots of proteoglycan, UNTIL the disc is markedly degenerated, at which point the annulus loses the ability to manufacture proteoglycans. See Liu Spine. 2001 Jan 15;26(2):134-41.

Why do we care? The answer is that in spinal cord injury, we want to know ALL the candidates which might be causing pain. Of late, it has appeared that wherever there is inflammation, there is pain, and wherever there is pain, there is inflammation.

And so we look at EVERY proinflammatory. Significantly, proteoglycans are exactly that, proinflammatory. When cracks appear in the annulus surrounding the disc, allowing proteglycans to escape, inflammation surrounding the area can be demonstrated.

It has been opined that diseases of surrounding ligaments, such as ossification of the posterior longitudinal ligament are the result of unconfined proteoglycans and the inflammation they cause. Why are some herniations painful and others not? The answer must lie in the biochemical milieu and the residual metabolic ability of the disc to synthesize proinflammatory molecules.

Recently it was even possible to find nitric oxide (NO) in the spinal fluid of those with degenerated discs. NO is of course directly linked to reactive oxygen species (ROS), which are at the core of inflammation, which leads to pain.

Kang has shown in Spine. 1995 Nov 15;20(22):2373- 8.that “intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2″. You will recognize these as pain chemicals. Matrix metalloproteinases (MMP) can be thought of as increasing vascular permeability so nitric oxide can pass through more easily and do its job of arresting proteoglycan production, and actually degrading the polymer.

We therefore cannot ignore proteoglycans, even though for many years they were dismissed as mainly a structural component of parts of the central nervous system. The body is VERY economical in how it uses molecules. Everything is multiuse. Nothing seems to function as an island unto itself.

A matrix protein is a protein which provides support of tissue, such as in collagen. Collagen sometimes provides support for tissue that would otherwise be loose or prone to loss of form. Proteoglycans are found along neurons in the central nervous system. As stated, when released they are proinflammatory. It would appear that when the body breaks down, the apoptotic (programmed cell death) system kicks into gear. ROS largely performs this task. Release of cell killing reactive oxygen species is accompanied by inflammation, which is behind pain.

Proteoglycans are structural matrix proteins. A polymer is a long chain of repeating units. Proteoglycans are polymers of amino acids and disaccharides.

Chondroitin sulfate is an important part of cartilage. Linked with chondroitin sulfate, proteoglycan behaves oddly. Chondroitin sulfate proteoglycan, which occurs naturally in the cord area, has been found to be a potent INHIBITOR of repair and an evoker of inflammation.

This is something of a contradiction, a proinflammatory which inhibits repair. It is as if proteoglycan, a support protein, is all about destruction, disallowing repair. This is not intuitive.

Picture cord injury as being followed by lots of proteoglycan, with resultant inflammation and failure of axonal regrowth.

Rolls et al reported in Jan 5 FASEB Article doi:10.1096/fj.05-4540fje that a fraction of chondoitin sulfate proteoglycan (CSPG), a degredation product of the original matrix protein (CSPG-DS), can interfere with the parent product. This fraction is a disaccaride which is known as CSPG-DS. This substance suppressed TNF alpha after cord injury. CSPG-DS also decreased NF Kappa B, the transcription factor. You will need to have read preceding articles to get a handle on TNF alpha and NF Kappa B, which are related to neuroinflammation

Basically, inflammation associated with neuronal injury is being supressed by CSPG-DS. The authors in the FASEB article suggested that injection of CSDS-DS into spinal fluid at the time of injury might prevent inflammatory sequellae. Since central pain is viewed as an inflammatory sequella to certain cord injury, here is a potential for possible therapy of the cord injured. It may also replace some surgery which has been performed for the pain of a herniated disc.