Spinal cord trauma and the molecular point of no return.
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.
Centre 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
Ping K
PK
Yip
Andrea
A
Malaspina
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors