Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process. However, no study has specifically addressed whether fecal microbiota transfer (FMT) attenuates neurologic deficits after TBI. ⋯ These data suggest that restoring a pre-injury gut microbial community structure may be a promising therapeutic intervention after TBI.
-
Sepsis is a fatal health issue induced by an aberrant host response to infection, and it correlates with organ damage and a high mortality rate. Endothelial barrier dysfunction and subsequent capillary leakage play major roles in sepsis-induced multiorgan dysfunction. Anaerobic glycolysis is the primary metabolic mode in sepsis and the pyruvate dehydrogenase complex (PDHC) serves as a critical hub in energy regulation. ⋯ The LPS-treated HUVEC model showed that DCA reversed LPS-induced phosphorylation of pyruvate dehydrogenase E1α Ser293 and Ser300 to restore PDHC activity. Immunoprecipitation results showed that LPS treatment increased the acetylation level of PDH E1α in HUVECs. Our study suggested that activation of PDHC may represent a therapeutic target for treatment of LPS-induced endothelial barrier dysfunction.
-
"Endotheliopathy of trauma" is recognized as endothelial dysfunction following traumatic injury leading to poor patient outcomes. Acute post-traumatic disruptions in endothelial cell function have been associated with profound physiologic, hemodynamic, and coagulation derangements. The goal of this study was to define the generation and extent of endotheliopathy in murine polytrauma models by evaluating the post-traumatic release of serum biomarkers of ongoing cellular injury. ⋯ A murine model of polytrauma including TBI, hemorrhagic shock, and laparotomy abdominal crush is a reliable method for evaluation of endotheliopathy secondary to trauma as indicated by differential changes in serum biomarkers.