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Published on: December 31, 2017
Spinal cord trauma and the molecular point of no return
1Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK. p.yip@qmul.ac.uk
Abstract:
A mechanical trauma to the spinal cord can be followed by the development of irreversible and progressive neurodegeneration, as opposed to a temporary or partially reversible neurological damage. An increasing body of experimental and clinical evidence from humans and animal models indicates that spinal cord injury may set in motion the development of disabling and at times fatal neuromuscular disorders, whose occurrence is not normally associated with any major environmental event. This outcome appears to be dependent on the co-occurrence of a particular form of mechanical stress and of a genetically-determined vulnerability. This increased vulnerability to spinal cord injury may depend on a change of the nature and of the timing of activation of a number of neuroprotective and neurodestructive molecular signals in the injured cord. Among the main determinants, we could mention an altered homeostasis of lipids and neurofilaments, an earlier inflammatory response and the failure of the damaged tissue to rein in oxidative damage and apoptotic cell death. These changes could force injured tissue beyond a point of no return and precipitate an irreversible neurodegenerative process. A better knowledge of the molecular signals activated in a state of increased vulnerability to trauma can inform future treatment strategies and the prediction of the neurological outcome after spinal cord injury.
Insights
Spinal cord injury can lead to irreversible neurodegeneration, especially in genetically vulnerable individuals. Understanding molecular signals is key to predicting outcomes and developing treatments for these debilitating neuromuscular disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Trauma Research
Background:
- Mechanical trauma to the spinal cord can cause irreversible neurodegeneration.
- This outcome is linked to genetic vulnerability and specific mechanical stress.
- Spinal cord injury may trigger disabling neuromuscular disorders.
Purpose of the Study:
- Investigate the molecular mechanisms underlying irreversible neurodegeneration after spinal cord injury.
- Identify factors contributing to increased vulnerability to spinal cord trauma.
- Inform future treatment strategies and outcome prediction.
Main Methods:
- Analysis of experimental and clinical evidence from human and animal models.
- Examination of molecular signals (neuroprotective and neurodestructive) in injured spinal cords.
- Assessment of changes in lipid and neurofilament homeostasis, inflammation, oxidative stress, and apoptosis.
Main Results:
- Increased vulnerability depends on altered timing and nature of molecular signal activation.
- Key determinants include altered lipid/neurofilament homeostasis, early inflammation, and impaired control of oxidative damage and apoptosis.
- These factors can push injured tissue beyond a point of no return, leading to irreversible neurodegeneration.
Conclusions:
- Understanding molecular signals in vulnerable individuals is crucial for managing spinal cord injury.
- Identifying these signals can guide the development of targeted therapies.
- This knowledge aids in predicting the long-term neurological prognosis after spinal cord trauma.
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