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Spinal Cord Injury: Progress, Promise, and Priorities
MONITORING REAL-TIME PROGRESSION OF SPINAL CORD INJURIES
It is hoped that in the near future biomarkers will be available for diagnosis or prediction of the clinical course of an individual after a spinal cord injury; however, no biomarkers are currently available to identify the changes occurring in the cells in the living spinal cord, such as neurite outgrowth, cell death, or changes in gene expression. Researchers have identified a large number of potential biomarkers (Table 3-6) and are developing practical methods to assess changes to those markers that could be used in the clinical setting. Once biomarkers are available and validated, they could be used to aid researchers and clinicians with making a diagnosis and establishing a prognosis, monitoring changes over time, and evaluating therapeutic interventions.
Trauma to the spinal cord affects a large number of biochemical cascades and reactions, but specific details about the genes involved in these processes are not well understood. Most of these changes are reflected by changes in mRNA and protein levels (Table 3-7). Since mRNA is copied, or transcribed, from DNA and provides the transcript that the cell uses to synthesize new proteins, analysis of mRNA or protein levels could reveal information about changes in cellular events. Advances in microarray technologies over the last decade have made it possible for researchers to examine the expression patterns of hundreds, if not thousands, of genes at the same time by comparing changes in gene activity in spinal cord samples from healthy and injured individuals. Using biomarkers, microarrays, and other tools, investigators have started to assess the complexity of the biological response to spinal cord injury. The full potential uses of biomarkers for spinal cord injury research include the following:
Diagnosis and prognosis. The expression profile of a biomarker, especially proteins, could provide clinicians with information that aids in establishment of a diagnosis and a prognosis of a patient’s injury. For instance, the progression of multiple sclerosis (MS) can be determined by examining the levels of a major myelin component, myelin basic protein, whose concentration increases in the cerebrospinal fluid in response to a demyelinating episode. Experiments with laboratory animals have identified similar gene expression fluctuations in response to spinal cord injuries. For example, the onset of the acute immune response is characterized by increases in the levels of the interleukin-6 protein (Segal et al., 1997; Carmel et al., 2001; Song et al., 2001; Nesic et al., 2002), whereas apoptosis, or the controlled death of cells that begins in the secondary stage of the injury, is regulated, in part, by changes in the levels of the Fas protein (Li et al., 2000;