Education: Inflammation-Chicken or Egg, Friend or Foe?

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It is believed that progressive MS is associated with nerve damage. As shown by The nerve gets damaged ( myelin is red and the nerve is green when it is myelinated the colours merge and appear yellow = green + red) and cut and the end of the nerve bleds into a ballon as the contents such a amyloid precurosor protein (APP) of the nerve continue to get transported down the nerve. The stump below the cut then dies and degenerates.
This picture from the Lab of Bruce Trapp is the Brooklyn bridge of Neuroprotection papers.
(Every time you see a film in New York,Manhattan you always get a shot of the Brooklyn Bridge)

These axon transections are found in areas where there is active inflammation as shown by the Trapp Lab. If you remember the types of lesion as shown in Expresso pathology by Dr.Love
______________________________________________________________
Tissue…………………………………………………..Number of axonal Transections
______________________________________________________________

Control white matter……. less than 1 transection per square millimeter (1mm x 1 mm)
(No inflammation)

Core of Chronic Lesion……………….. 875 transections per square millimeter
(Inflammation has largely gone)

Edge of Chronic Active Lesion….About 3,000 transections per square millimeter
(inflammation present)

Active Lesion………………………..About 11,000 transections per square millimeter
(Very active inflammation)

______________________________________________________________

Inflammation is about getting rid of the trigger of damage and then repairing the area of damage. (Unfortunately the CNS is not great at repair). Now you can look at this and wonder if inflammation is part of the cause of the damage, which you can show in cell culture systems.

However, there are a few people who think that inflammation is present because it is clearing up the damage from some other cause. Some call this “Protective immunity”. If you believe in the former you try and stop the inflammation and aim to protect nerves from further damage or if you believe in the latter you do NOTHING about the inflammation or even try to augment this, as the nerves are doomed anyway and you should be able to find areas of marked nerve transections without inflammation (which does not appear to be the case, such as found when you do bone marrow transplants and the recipients unfortunately dies or the early lesions) and that immune suppression should do nothing or make disease worse (which it does not usually appear to do).

Whilst this inflammation can mean T and B cells to some and macrophage and microglial reactions to others, I think it is prudent to try and do SOMETHING and investigate this rather than do NOTHING, when clearly sticking you head in the sand or worse, will result in no progress and Nothing will change.

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MouseDoctor

3 comments

  • Regeneration is rapid in PNS (up to 1 millimeter a day of regrowth) because Schwann cells are better at repairing than Oligodendrocytes. Therefore, why can we not get Schwann cells into the CNS and get them to repair damage to axons?

  • The PNS and CNS are entirely different environments, the CNS is sealed off from the rest of the body by the Blood:Brain barrier. The CNS tries to maintain homeostasis at all costs including the regeneration seen in the peripheral nervous system.

  • Schwann cells can sometimes get into CNS and repair, but there has been a study in a few MSers using Schwann cell transplants and the studies were dropped and probably failed.

    However the lack of regrowth of central nervous system nerves is not because of lack of schwann cells but there are growth inhibitors found in the central nervous system. These is a clinical development of an inhibitor to block at least one of these.

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