Military Personnel with Chronic Symptoms Following Blast Traumatic Brain Injury Have Differential Expression of Neuronal Recovery and Epidermal Growth Factor Receptor Genes

• Main Authors: Morgan eHeinzlemann, Swanaralatha Y Reddy, Hwyanhwa eLee, Louis eFrench, Vincent eMysliwiec, Tristin eBaxter, Taura eBarr, Jessica Mary Gill
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2014-10-01
• Series: Frontiers in Neurology
• Subjects: Blast Injuries; Ubiquitin; Traumatic brain injury (TBI); gene-expression; post concusive disorder
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00198/full

Objective: Approximately one-quarter of military personnel who deployed to combat stations sustained one or more blast-related, closed-head injuries. The mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI), and place military personnel at high risk for chronic symptoms of post-concussive disorder (PCD), post-traumatic stress disorder (PTSD), and depression are not elucidated.Methods: To investigate the mechanisms of persistent blast related symptoms, we examined expression profiles of transcripts across the genome to determine the role of gene activity in chronic symptoms following blast-TBI. Active duty military personnel with (1) a medical record of a blast-TBI that occurred during deployment (n=19) were compared to control participants without TBI (n=17). Controls were matched to cases on demographic factors including age, gender and race, and also in diagnoses of sleep disturbance, and symptoms of PTSD and depression. Due to the high number of PCD symptoms in the TBI+ group, we did not match on this variable. Using expression profiles of transcripts in microarray platform in peripheral samples of whole blood, significantly differentially expressed gene lists were generated. Statistical threshold is based on criteria of 1.5 magnitude fold-change (up or down) and p-values with multiple test correction (false discovery rate; FDR<0.05). Results: There were 34 transcripts in 29 genes that were differentially regulated in blast-TBI participants compared to controls. Up-regulated genes included epithelial cell transforming sequence and zinc finger proteins, which are necessary for astrocyte differentiation following injury. Tensin-1, which has been implicated in neuronal recovery in preclinical TBI models, was down-regulated in blast-TBI participants. Protein ubiquitination genes, such as epidermal growth factor receptor, were also down-regulated and identified a