Molecular mechanisms of axonal damage in inflammatory central nervous system diseases.
OBJECTIVE
Axonal dysfunction and damage is an early pathological sign of autoimmune central nervous system disease, viral and bacterial infections, and brain trauma. Axonal injury has attracted considerable interest during the past few years because the degree of axonal damage appears to determine long-term clinical outcome.


RESULTS
Advanced magnetic resonance spectroscopic imaging techniques have suggested that axonal loss and dysfunction is responsible for the persistent neurological deficits that occur in patients with multiple sclerosis. Histopathological methods have shown that axonal damage is defined primarily by dysfunction of axonal transport, and finally by complete transection and degeneration of axons. Recent studies have demonstrated that the extent of axonal damage in the primary demyelinating lesion of multiple sclerosis patients is associated with the number of activated microglia/macrophages and cytotoxic CD8+ T lymphocytes. In addition, diffuse axonal dysfunction independent of demyelination develops in normal appearing white matter, possibly due to indirect effects of inflammation.


CONCLUSIONS
The fact that axonal damage in response to overt inflammatory reactions may occur gradually, leaving a window for therapeutical intervention, has important clinical implications. Determination of the exact molecular mechanism might help in finding new therapies for inflammatory axonal damage.
Neumann
Harald
H
Neuroimmunology Unit, European Neuroscience Institute Göttingen, Göttingen, Germany. hneuman1@gwdg.de
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000378:metabolism / Q000473:pathology; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D020806:Central Nervous System Bacterial Infections / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000378:metabolism* / Q000473:pathology*; D020805:Central Nervous System Viral Diseases / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D017628:Microglia / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism*