Abstract
One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.
Highlights
It is estimated that over 30,000 people in Canada, and approximately ten times that many in the USA, are living with spinal cord injury (SCI), and more than 1,000 and 11,000 new cases occur annually in Canada and the USA, respectively.Improvements in the medical, surgical, and rehabilitative care have dramatically extended the lifespan and increased the quality of life of individuals with acute and chronic SCI, but much remains to be improved in restoring function for individuals with SCI
The current clinical measures for characterizing injury severity are based on functional tests that cannot be relied upon immediately following injury because they are often compromised by shock, other attendant injuries and drugs or alcohol
Rats receiving contusion injuries targeted at C4/C5 with displacement set to 1.3-mm yielded an average force recording of 155.765.0 Kdynes
Summary
It is estimated that over 30,000 people in Canada, and approximately ten times that many in the USA, are living with spinal cord injury (SCI), and more than 1,000 and 11,000 new cases occur annually in Canada and the USA, respectively (http:// rickhansenregistry.org; https://www.nscisc.uab.edu).Improvements in the medical, surgical, and rehabilitative care have dramatically extended the lifespan and increased the quality of life of individuals with acute and chronic SCI, but much remains to be improved in restoring function for individuals with SCI. Little can be done about the primary mechanical damage to the spinal cord that occurs on impact. Most spinal cord injuries are anatomically incomplete and the secondary parenchymal damage contributes significantly to the final extent of neural damage and to the extent of the long term disability [1,2,3]. Due to its prolonged nature, this secondary injury is amenable to treatment, and a number of candidate neuroprotective interventions that may potentially halt or attenuate the secondary damage have been developed [4]. The severity of the initial injury likely plays a significant role in determining the nature and amplitude of the secondary response and the appropriate interventions. The current clinical measures for characterizing injury severity are based on functional tests that cannot be relied upon immediately following injury because they are often compromised by shock, other attendant injuries and drugs or alcohol
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