Induction of activating transcription factor 3 (ATF3) in the cerebral cortex of a mouse model of blast-induced traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of long-term disabilities and mortality worldwide. Blast-induced TBI (bTBI) is the injury most commonly sustained by military personnel, but the pathomechanisms are largely unknown. Recently, accumulating evidence has suggested that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators such as interleukins, cytokines, and chemotactic cytokines (chemokines), is a key pathological feature in bTBI. Therefore, controlling excessive neuroinflammation is critical to improve long-term neurological outcomes after bTBI, so understanding the mechanism of the neuroinflammation in bTBI is of significant interest. Activating transcription factor 3 (ATF3) is one of the most important transcription factors that regulate local and systemic inflammation in multiple pathophysiological processes such as cardiovascular disease, dementia, and ischemia/reperfusion-induced damage. Recently, ATF3 has attracted much attention for involvement in the neuroinflammatory response, by regulating the production of neuroinflammatory mediators, in a weight-drop-based TBI model. In this model, the upregulation of Atf3 messenger ribonucleic acid (mRNA) levels was rapidly induced with the strongest increase at 1-2 h and decline by 4 h post-injury. However, there is little information about ATF3 in bTBI, and thus, the present study examined the expression of ATF3 in a mouse bTBI model. We here show the significant upregulation of Atf3 mRNA was not observed in the cerebral cortex at 2 h post-exposure. However, the upregulation was observed at 5 days post-injury. Our results suggest robust differences in time course of neuroinflammation between other non-blast and blast TBIs.