Inhibition of BRD4 expression attenuates the inflammatory response and apoptosis by downregulating the HMGB-1/NF-κB signaling pathway following traumatic brain injury in rats

Pattern diagram of BRD4 regulation of neuroinflammation after brain injury. TBI induces a rapid increase in BRD4 expression.BRD4 can activate HMGB-1/NF-κB pathway, promote the activation of Microglia and the release of neuroinflammatory factors, and lead to neuronal apoptosis. [Display omitted] •Our research demonstrated that expression of BRD4, HMGB-1, and nuclear factor-kappa B (NF-κB) protein was increased significantly around the cortical-lesion area after brain injury.•BRD4 may have a proinflammatory role in secondary brain injury through the HMGB-1/NF-κB signaling pathway.•Inhibition of BRD4 expression may play a part in secondary brain injury and BRD4 could be targeted therapy strategy for brain injury. Neuroinflammation plays an important part in secondary traumatic brain injury (TBI). Bromodomain-4 (BRD4) exerts specific proinflammatory effects in various neuropathological conditions. However, the underlying mechanism of action of BRD4 after TBI is not known. We measured BRD4 expression after TBI and investigated its possible mechanism of action. We established a model of craniocerebral injury in rats. After different intervention measures, we used western blotting, immunofluorescence, real-time reverse transcription-quantitative polymerase chain reaction, neuronal apoptosis, and behavioral tests to evaluate the effect of BRD4 on brain injury. At 72 h after brain injury, BRD4 overexpression aggravated the neuroinflammatory response, neuronal apoptosis, neurological dysfunction, and blood-brain-barrier damage, whereas upregulating expression of HMGB-1 and NF-κB had the opposite effect. Glycyrrhizic acid could reverse the proinflammatory effect of BRD4 overexpression upon TBI. Our results suggest that: (i) BRD4 may have a proinflammatory role in secondary brain injury through the HMGB-1/NF-κB signaling pathway; (ii) inhibition of BRD4 expression may play a part in secondary brain injury. BRD4 could be targeted therapy strategy for brain injury.