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Electrically active axons degenerate when exposed to nitric oxide.
K J Smith1, R Kapoor, S M Hall
1Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, London, United Kingdom. kenneth.smith@kcl.ac.uk
Annals of Neurology
|April 20, 2001
Summary
Inflammatory neurological diseases like multiple sclerosis may cause permanent nerve damage. This study shows that nitric oxide (NO) combined with nerve impulse activity can lead to axonal degeneration, contributing to disability.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Axonal degeneration is a primary cause of permanent neurological deficits in inflammatory conditions such as multiple sclerosis.
- Inflammatory lesions are sites where axons degenerate, suggesting localized inflammatory factors are responsible.
- Nitric oxide (NO) has been previously identified as a factor causing reversible axonal conduction block.
Purpose of the Study:
- To investigate if nitric oxide (NO) can induce axonal degeneration under physiological conditions.
- To determine the role of impulse activity in NO-mediated axonal damage.
- To explore the mechanisms underlying permanent disability in neuroinflammatory disorders.
Main Methods:
- Rat dorsal roots were exposed in vivo to nitric oxide (NO) and sustained impulse activity at varying frequencies (1, 50, or 100 Hz).
- Morphological examination was performed to assess nodal and paranodal changes indicative of degeneration.
- Experiments were prolonged in some cases to observe later stages of degeneration, including myelin ovoids and axonolysis.
Main Results:
- Exposure to low micromolar concentrations of NO alongside sustained impulse activity at 50 or 100 Hz induced nodal and paranodal changes consistent with acute wallerian degeneration.
- In prolonged experiments, over 95% of fibers showed myelin ovoids and axonolysis when stimulated at physiological frequencies (50 or 100 Hz) in the presence of NO.
- Axons stimulated at 1 Hz in the presence of NO did not exhibit signs of degeneration.
Conclusions:
- The combination of physiological impulse activity and nitric oxide (NO) at inflammatory sites can trigger axonal degeneration.
- Electrical activity in axons may be a critical factor contributing to irreversible nerve damage and permanent disability in neuroinflammatory diseases.
- Findings suggest a novel mechanism for axonal damage in conditions like multiple sclerosis, highlighting the interplay between inflammation and neuronal activity.