Spinal cord injury (SCI) is one of the most devastating conditions that deeply affects the patient's quality of life. The acute stage of the injury mechanism remains a fairly understudied area containing many potential therapeutic targets for a better functional recovery. In this study we aimed to explore the proliferative aspect of the acute stage of SCI. We approached it using an epigenetic perspective focusing on the role of BET proteins in the injury's pathophysiology. BET proteins have become increasingly clinically relevant as proliferation targets for several diseases such as cancer, atherosclerosis, and liver fibrosis. Thus, we hypothesized that inhibiting BET epigenetic proteins would lead to reduced proliferation in the injury. We used I-BET151 as an inhibitor, as well as Brd4 knockout models in order to study whether these proteins also have a role mediating cellular proliferation in SCI. We used EdU Click technology to mark the cells proliferating at 3 days post injury (dpi). We also used immunohistochemistry to get a better understanding of cell-specific effects. We found that BET proteins do not mediate proliferation in the acute stage of SCI. However, the inhibition of BETs lead to a decrease in immune cell infiltration. These results were validated with the use of Brd4 genetic deletion model specific for myeloid cells. This study adds to the knowledge gap in the acute phase of SCI and points towards future research that may result in discovering a novel therapeutic target for recovery.
