Proteomic Analysis post Acute Spinal Cord Injury in human Oduwole KO, Lang A, Chukwuyerenwa K, Mccormack DJ, Poynton A, Republic of Ireland  

Background Spinal cord injury (SCI) is a leading cause of permanent disability in young adults, resulting in partial or complete loss of motor and sensory function. Treatment options are currently limited to preventing injury due to breakdown of the extracellular matrix by protein enzymes. These proteins are expressed in serum in a time- dependent fashion.

Aims of the study 1. To identify potential biomarker that can be used as prognostic index to monitor progress after spinal cord injury. 2. Identify a novel protein that will provide the basis for new targets in therapeutic treatment of spinal cord injury patients.

Method Study cohort included patients with complete (n=10) or incomplete (n=5) spinal cord injuries, and patients with simple diaphyseal tibia fracture (n=5). The control group (n=2) consisted of healthy volunteers without clinical symptoms. Serum samples were collected at three- time points following acute injuries. The differences in protein expression between the four groups of patients were analysed using two dimensional fluorescence differences in gel electrophoresis (2D-DIGE).

Results Among Group A patients (Complete spinal cord injury-analysis 1), the up- and down-regulated protein spots that exhibited 1.5-fold difference signal intensity with statistical significance (p<0.05, t-test, confidence intervals 95%) were 75. Up-regulated proteins (n=54) were found superior in number than the down-regulated proteins (n=21). For protein expression between 24hr and day 5 time points, 15 protein spots were significantly up regulated while 2 spots were down regulated.

Results For Group B patients, (central cord syndrome) down-regulated spots are more predominant (n=43) than up-regulated proteins (n=21). There was only one up-regulated spot between the day 1 and day-5 time points. Clinical correlation of the patients in this group revealed full functional recovery in all. In Group C patients, the number of up-regulated (n=9) proteins almost equals the down-regulated ones (n=11).

Clinical interpretation The above results suggest a direct relationship between the level of up-regulated protein spots and severity of injury. The appearances of unique protein spots are also related to injuries related to spinal cord.

Clinical interpretation Patients with functional recovery had no unique protein spots between these two-time points. Two-time point analysis also show that patient with no functional recovery had both increased number of unique spots and more up-regulated proteins

Future study We hypothesed that up-regulated proteins between time points may be contributing to secondary spinal cord injury. After protein identifications, further studies to examine possibility of developing inhibitors are justified. against up-regulated proteins or stimulator for the down-regulated ones will be justified.