Intravenously Infusing the Secretome of Adipose-Derived Mesenchymal Stem Cells Ameliorates Neuroinflammation and Neurological Functioning After Traumatic Brain Injury.

The secretome of mesenchymal stem cell (MSC) offers a series of immunoregulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. After the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST through caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were reduced, whereas transforming growth factor-beta (TGF-ß) and tumor necrosis factor-stimulated gene 6 protein (TSG-6) levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.

[Effect of ulinastatin in traumatic brain injury with multiple injuries].

OBJECTIVE: To investigate the effect of ulinastatin (UTI) in traumatic brain injury (TBI) with multiple injuries. METHODS: A prospective analysis of TBI patients with multiple injuries was performed. Sixty cases of cranial trauma with multiple injuries patients were randomly divided into two groups. There were 28 cases in control group while 32 cases in treatment group. Control group underwent conventional treatment while intravenous infusion of UTI was performed in treatment group. The dose of UTI was 200 kU every 8 hours. Patients' intracranial cerebral pressure (ICP) were monitored at admission and 10 days after treatment. At the same time levels of white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate amino transfer enzymes (AST), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), interleukin (IL-2, IL-6) were detected. RESULTS: ICP was down trend after treatment in UTI group, but there was no statistical difference compared with the control group. Hepatic and renal function and inflammation factor levels were significantly decreased in both groups. WBC, CRP, PCT, ALT, AST, Cr, BUN, TNF-α, IL-2, IL-6 were significantly lower in UTI group than those in control group (WBC:12.3±4.5×10(9)/L vs. 15.9±6.3×10(9)/L, CRP:46.12±11.47 mg/L vs. 64.24±18.31 mg/L, PCT:4.51±1.27 µg/L vs. 10.51±4.27 µg/L, ALT:47.26±8.23 U/L vs. 60.94±8.39 U/L, AST:42.67±7.63 U/L vs. 68.51±10.17 U/L, Cr:79.62±15.36 µmol/L vs. 102.36±16.82 µmol/L, BUN:6.35±2.36 mmol/L vs. 8.39±1.67 mmol/L, TNF-α:93.6±31.5 µg/L vs. 195.8±23.9 µg/L, IL-2:12.3±4.5 µg/L vs. 15.9±6.3 µg/L, IL-6:52.36±12.46 µg/L vs. 69.34±26.13 µg/L, all P<0.05). The incidence of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) in UTI group were significantly lower than those in control group (21.88% vs. 46.43%, 9.38% vs. 28.57%, both P<0.05). CONCLUSION: Application of UTI treatment in TBI with multiple trauma patients can potentially protect the brain, liver and other organ function, thus significantly reduce incidence rate of SIRS and MODS by reducing the release of inflammatory mediators and systemic reaction to the trauma invasion.