Hypertonic saline maintains coagulofibrinolytic homeostasis following moderate‑to‑severe traumatic brain injury by regulating monocyte phenotype via expression of lncRNAs.
Traumatic brain injury (TBI) is the most common cause of death and permanent disability in people aged <45, and is associated with secondary brain injury and bleed progression, resulting in increased morbidity and mortality. TBI may also induce innate host defense responses characterized by activation of resident microglia and astrocytes, brain microvascular endothelial cells and peripheral blood monocytes. In the present study, 34 patients with moderate‑to‑severe traumatic brain injury were randomly divided into two groups, including a 7.5% hypertonic saline (HS) treatment group (4 ml/kg) and 3% HS treatment group (4 ml/kg). The results demonstrated that treatment with 7.5% HS decreased the intracranial pressure and improved coagulofibrinolytic homeostasis. Analysis of the monocyte subsets revealed significant reduction in the proportion of cluster of differentiation (CD)14++CD16+ circulating inflammatory monocytes in the 7.5% HS group. In addition, 7.5% HS treatment downregulated the expression of long non‑coding (lnc) RNA2448‑11 and lncRNA1403 in the peripheral blood mononuclear cells of patients with TBI. Using reverse transcription‑quantitative polymerase chain reaction, it was determined that 7.5% HS regulated the expression of tumor necrosis factor‑α, interleukin‑1β, transforming growth factor‑β and thrombomodulin, which are the target genes of lncRNA2448‑11 and lncRNA1403. These results indicated that 7.5% HS improved the intracranial pressure and coagulofibrinolytic homeostasis by modulating the phenotype of monocytes through lncRNA2448‑11 and lncRNA1403. These findings provided evidence that initial resuscitation with HS imparts functional changes to inflammatory cells following TBI, thereby reducing potential neuroinflammatory events associated with secondary brain injury.
|Authors:||Yang X, Chen Y, Li J, Chen L, Ren H, Liu Y, Zhang X.|
|Journal:||Mol Med Rep. 2019 Feb;19(2):1083-1091|
|PubMed:||Find in PubMed|