Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and is Linked to Insufficient Neuronal Recovery Detected through MRI

Authors

• Y Cho
• L Latour
• H Kim
• A Olivera
• W Livingston
• C Lai
• J Gill
• A Cashion

Abstract

Background: Age plays a critical role in recovery from traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. Objective: This study was undertaken to investigate the relationship of age on gene-activity following a TBI. Methods: Two groups were compared on global gene-activity at 48 hours following a TBI, and then at follow-up within 1-week of the TBI. The younger group was between the age of 19-35 years, and the older group was between the age of 60-89 years. In each group, gene expression profiles, and imaging findings from magnetic resonance imaging (MRI) and computed tomography (CT) were compared. Results: Gene expression at 48hrs and 1-week revealed significant up-regulation in 42 genes including noggin (NOG), basic leucine zipper transcription factor 2 (BACH2),leucine rich repeat neuronal 3 (LRRN3) and lymphoid enhancer-binding factor 1(LEF1) in the young group compared to the older group. In contrast, the older group showed 5 up-regulated genes including S100 calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8) compared to the younger group.Moreover, MRI findings revealed that a larger percentage of subjects with MRI+ in TBI at baseline converted to MRI in TBI at 1-week in the young group compared to the old group (p=0.003). Conclusions: Together, these data indicate that age impacts gene-activity following a TBI, and suggests that this differential activity contributes to poor recovery in older patients as indicated through neuroimaging.

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