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Hypertrophic scar (HTS) occurs frequently after burn injury. Treatments for some aspects of scar morbidity exist, however, dyspigmentation treatments are lacking due to limited knowledge about why scars display dyschromic phenotypes. Full thickness wounds were created on duroc pigs that healed to form dyschromic HTS. HTS biopsies and primary cell cultures were then used to study pigmentation signaling. Biopsies of areas of both pigment types were taken for analysis. At the end of the experiment, melanocyte-keratinocyte cocultures were established from areas of differential pigmentation. Heterogeneously dyspigmented scars formed with regions of hyperpigmentation and hypopigmentation. Melanocytes were present in both pigment types measured by S100ß quantitative real time-polymerase chain reaction (qRT-PCR) and immunostaining, and visualized by dendritic cell presence in primary cultures. P53 expression was not different between the two pigment types. Hyperpigmented scars had upregulated levels of proopiomelanocortin (POMC), adrenocorticotropic hormone (ACTH), a-melanocyte stimulating hormone (a-MSH), stem cell factor (SCF), and c-KIT and melanocortin 1 receptors (MC1R) compared to hypopigmented regions. Many genes involved in dyspigmentation were differentially regulated by microarray analysis including MITF, TYR, TYRP1, and DCT. MiTF expression was not different upon further exploration, but TYR, TYRP1, and DCTwere upregulated in intact biopsies measured by qRT-PCR and confirmed by immunostaining. This is the first work to confirm the presence of melanocytes in hypopigmented scar using qRT-PCR and primary cell culture. An understanding of the initial steps in dyspigmentation signaling, as well as the downstream effects of these signals, will inform treatment options for patients with scars and provide insight to where pharmacotherapy may be directed.

High-voltage electrical injuries are a devastating form of trauma often treated in burn centers. Examining superficial wounds alone may lead to an inaccurate assessment of local, regional, and systemic severity of injury. In this work, the neurovasculature at sites regionally distinct from the contact wound were assessed for cellular pathology. Nine male Sprague–Dawley rats subjected to 1000 V direct-current shocks were separated into three groups: high-shock (>10-second contact), low-shock (<4-second contact), and control. Injury video was captured with a forward-looking infrared camera, and a thermal excitation analysis was performed. The neurovascular bundles from the iliofemoral region to the distal posterior tibial region were dissected from the hind limbs of the shocked animals and stained by immunohistochemistry for antibodies specific to apoptosis (APO) 1, caspase-3, activating transcription factor 3, high-mobility group box-1, granulocyte-macrophage colony-stimulating factor and interleukin-6. Real-time reverse-transcription polymerase chain reaction was used to quantify differential transcript levels of superoxide dismutases 1, 2, and 3 and heat-shock protein 70 from peripheral blood mononuclear cells and liver tissue. Finally, a protein array was used to identify key inflammatory cytokines in blood plasma. Significant dose-dependent trends were identified in apoptotic markers as well as inflammatory markers in both arterial and nerve tissues. Although arterial tissue exhibited a gradual decline in these markers proximally from the wound site, nerve tissue maintained a constant level at every location. Transcript analysis revealed an up-regulation of extracellular superoxide dismutase, and down-regulation of heat-shock protein 70, whereas plasma inflammatory cytokine levels indicated no significant changes. Thermal excitation analysis revealed a linear temperature increase, with a dose-dependent thermal maximum. In this study the authors have shown that neurovascular APO and inflammation are present at locations extremely proximal to electrical injury contact sites and this appears to be dose-dependent. Nerve tissue APO and inflammation may extend farther proximally than the iliofemoral region, and multiple proapoptotic mechanisms may be activated. No systemic inflammatory response was indicated in this study.

Mortality rates in burn patients increase if they experience complications of infection. Frequently, the organisms associated with such infections are Staphylococci, including antibiotic-resistant species such as methicillin-resistant Staphylococcus aureus. Virulence factor production can further complicate treatment as a localized toxin presence may derail the healing process and allow a more invasive infection, while a toxin that becomes systemic can induce shock and cause host immune disruption. Male rats were anesthetized and subjected to full-thickness burn wounds. One day postinjury, wounds were inoculated with Toxic Shock Syndrome Toxin-1-producing methicillin-resistant S. aureus. Animals were then divided into three treatment groups: vancomycin, linezolid, or positive control. For nine additional days, animals received twice-daily antibiotics and wound assessments, blood draws, and wound biopsies were performed. All animals had wound quantitative cultures that exceeded 1 × 108colony forming units (CFU) per gram 1 day after inoculation. Linezolid treatment significantly reduced the bacterial counts in the wounds. Positive controls and vancomycin-treated animals had toxins in their wounds by day 5 and this remained throughout the study (ranging from 20–80 ng/ml). Linezolid-treated animals had significant decrease in toxin production (< 5 ng/ml), and in most cases toxins were undetectable. No animals became systemically infected with bacteria at any point during the study. Superantigen production in burn wounds has morbid consequences in terms of long-term wound healing. A S. aureusburn wound infection model was created that allowed the study of the effect of two standard-use antibiotics on local burn wound pathophysiology. Most noteworthy is that low-dose linezolid arrested toxin production in the wound.

Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2–20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity.