Aims Cold stress has been shown to produce dramatic increases in 2-fluoro-2-deoxy-D-Glucose (18FDG) accumulation by brown adipose tissue (BAT) in rodents. However, neither the effects of other types of stress on 18FDG accumulation nor the effects of stressors on the accumulation of tracers of other aspects of energy metabolism have been evaluated. In this report we studied the effects of cold stress, burn injury, and cutaneous wounds on murine BAT at the macroscopic, microscopic, and metabolic level. Main Methods Glucose metabolism was studied with 18FDG, fatty acid accumulation was evaluated with trans-9(RS)-18F-fluoro-3,4(RS,RS)- methyleneheptadecanoic acid (FCPHA) and tricarboxcylic acid cycle (TCA) activity was evaluated with 3H acetate. Key Findings All three stressors produced dramatic changes in BAT at the macroscopic and microscopic level. Macroscopically, BAT from the stressed animals appeared to be a much darker brown in color. Microscopically BAT of stressed animals demonstrated significantly fewer lipid droplets and an overall decrease in lipid content. Accumulation of 18FDG by BAT was significantly (P <0.01) increased by all 3 treatments (Cold: ∼16 fold, burn ∼7 Fold and cutaneous wound ∼14 fold) whereas uptake of FDG by white fat was unchanged. This effect was also demonstrated non- invasively by μPET imaging. Although less prominent than with 18FDG, BAT uptake of FCPHA and acetate were also significantly increased by all three treatments. These findings suggest that in addition to cold stress, burn injury and cutaneous wounds produce BAT activation in mice. Significance This study demonstrates brown fat activated by several stressors leads to increased uptake of various substrates.
Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model.
It has been demonstrated that restoration of function to compromised tissue can be accomplished by transplantation of bone marrow stem cells (BSC) and/or embryonic stem cells (ESC). One limitation to this approach has been the lack of non-invasive techniques to longitudinally monitor stem cell attachment and proliferation. Recently, murine ESC lines that express green fluorescent protein (GFP), luciferase (LV) and herpes simplex thymidine kinase (HVTK) were developed for detection of actively growing cells in vivo by imaging. In the present study, we investigated use of these ESC lines in a burned mouse model using Integra® as a delivery scaffolding/matrix. Two different cell lines were used: one expressing GFP and LV and the other expressing GFP, LV and HVTK. Burn wounds were produced by application of a brass block (2 × 2 cm kept in boiling water prior to application) to the dorsal surface of SV129 mice for 10 seconds. 24 hrs after injury, Integra® with adherent stem cells was engrafted onto a burn wound immediately after excision of eschar. The stem cells were monitored in vivo by measuring bioluminescence with a CCD camera and immunocytochemistry of excised tissue. Bioluminescence progressively increased in intensity over the time course of the study and GFP positive cells growing into the Integra® were detected. These studies demonstrate the feasibility of using Integra® as a scaffolding, or matrix, for the delivery of stem cells to burn wounds, as well as the utility of bioluminescence for monitoring vivo cellular tracking of stably transfected ESC cells.
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