Binge Alcohol Exposure Modulates Rodent Expression of Biomarkers of the Immunoinflammatory Response to Orthopaedic Trauma

Sears, Benjamin W.; Volkmer, Dustin; Yong, Sherri; Himes, Ryan; Lauing, Kristen L.; Morgan, Michèle E.; Stover, Michael D.; Callaci, John J.

doi:10.2106/jbjs.j.00318

Cited by 14 publications

(15 citation statements)

References 32 publications

(57 reference statements)

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“…Hyper inflammatory responses can be activated by various types of serious injury, that is, hemorrhagic shock, multiple fractures, burns, chest trauma, brain injury, or a combination of injuries [8, 9, 27, 28]; furthermore, changes in cytokine levels are dependent on the degree of injury [29]. It seems that hip fractures, a low energy type of trauma, are insufficient to elicit significant physiologic alterations and immunological reactions.…”

Section: Discussionmentioning

confidence: 99%

“…Current reports indicate that surgery for a hip fracture should be performed as soon as possible to reduce postoperative complications and mortality [12–14]. To mimic the injury sustained due to this type of operation, proximal femoral intramedullary pinning was performed immediately following fracture according to Sears et al [9]. Prophylactic preoperative antibiotics (gentamicin, 5 mg/kg) were administered before incision.…”

Section: Methodsmentioning

confidence: 99%

“…A growing body of evidence suggests that severe trauma, such as burns, hemorrhagic shock, and polytrauma, induces the systemic release of various “danger signals” damage-associated molecular patterns (DAMPs) which leads to an overwhelming inflammatory response and subsequent indirect lung injury [6–9]. Similarly, we have demonstrated that hip fracture and surgery also elevate systemic proinflammatory mediators in elderly patients, and the inflammatory response may play an important role in postoperative liver and lung dysfunction [10].…”

Section: Introductionmentioning

confidence: 99%

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Systemic Inflammatory Responses and Lung Injury following Hip Fracture Surgery Increases Susceptibility to Infection in Aged Rats

Zhang

Sun

et al. 2013

Mediators of Inflammation

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Pulmonary infections frequently occur following hip fracture surgery in aged patients. However, the underlying reasons are not fully understood. The present study investigates the systemic inflammatory response and pulmonary conditions following hip fracture surgery as a means of identifying risk factors for lung infections using an aged rodent model. Aged, male Sprague-Dawley rats (8 animals per group) underwent a sham procedure or hip fracture plus femoral intramedullary pinning. Animals were sacrificed 1, 3, and 7 days after the injury. Markers of systemic inflammation and pulmonary injury were analyzed. Both sham-operated and injured/surgical group animals underwent intratracheal inoculation with Pseudomonas aeruginosa 1, 3, and 7 days after surgery. P. aeruginosa counts in blood and bronchoalveolar lavage (BAL) fluid and survival rates were recorded. Serum TNF-α, IL-6, IL-1β, and IL-10 levels and markers of pulmonary injury were significantly increased at 1 and 3 days following hip fracture and surgery. Animals challenged with P. aeruginosa at 1 and 3 days after injury had a significantly decreased survival rate and more P. aeruginosa recovered from blood and BAL fluid. This study shows that hip fracture and surgery in aged rats induced a systemic inflammatory response and lung injury associated with increased susceptibility to infection during the acute phase after injury and surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic Inflammatory Responses and Lung Injury following Hip Fracture Surgery Increases Susceptibility to Infection in Aged Rats

Zhang

Sun

et al. 2013

Mediators of Inflammation

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“…The surgery was performed immediately after fracture according to Sears et al [ 23 ]. Prophylactic preoperative antibiotics (gentamicin, 5 mg/kg) were administered before incision.…”

Section: Methodsmentioning

confidence: 99%

The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture

Gan

Zhong

Zhang

et al. 2015

Mediators of Inflammation

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Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as well as the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. After immediate surgery, the above variables were further increased. The serum mtDNA levels were significantly related with the serum cytokine (TNF-α and IL-10) levels and pulmonary histological score. In order to identify the meaning of mtDNA release following hip fracture, the elderly rats received injections with mtDNA. After treatment, the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. These results demonstrated that the immediate surgery increased the mtDNA release that could aggravate systemic inflammatory response and lung injury induced by elderly hip fracture; serum mtDNA might serve as a potential biomarker of systemic inflammatory response and lung injury following elderly hip fracture.

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“…Impaired fracture healing related to alcohol exposure is a pathophysiologically relevant alternative for studying fracture repair. Preclinical studies have demonstrated that alcohol exposure impedes fracture callus composition and biomechanical strength[7] and modulates the immunoinflammatory response to blunt orthopaedic trauma[8]. …”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Facilitate Fracture Repair in an Alcohol-Induced Impaired Healing Model

Obermeyer¹,

Yonick

Lauing

et al. 2012

Journal of Orthopaedic Trauma

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Objectives Clinical studies have shown alcohol to be a risk factor for traumatic orthopaedic injuries and for nonunion. Data from animal studies suggest that alcohol exposure inhibits fracture healing. This report presents a novel rodent model of impaired fracture healing caused by repeated alcohol exposure. Using this model, we examined the regenerative effects of an intravenously administered population of isolated and expanded MSCs on fracture healing. Methods Bone marrow-derived MSC were isolated from transgenic Green Fluorescent Protein (GFP) C57BL/6 mice and culture expanded using a lineage depletion protocol. Adult wild-type C57BL/6 mice were subjected to a two-week binge alcohol exposure paradigm, (3 days during which they received daily intraperitoneal injections of a 20% alcohol/saline solution followed by a four-day rest period and another 3 consecutive day binge cycle. At completion of the second binge cycle, mice were subjected to a midshaft tibia fracture while intoxicated. Twenty-four hours following fracture, animals were administered an intravenous (IV) transplant of GFP-labeled MSC. Two weeks following fracture, animals were euthanized and injured tibiae were collected and subjected to biomechanical, histologic, and micro-computed tomography analysis. Results Pre-injury binge alcohol exposure resulted in a significant impairment in biomechanical strength and decrease in callus volume. MSC transplants restored both fracture callus volume (p<0.05) and biomechanical strength (p<0.05) in animals with alcohol-impaired healing. In vivo imaging demonstrated a time-dependent MSC migration to the fracture site. Conclusions These data suggest that a two-week binge alcohol exposure significantly impairs fracture healing in a murine tibia fracture model. IV-administered MSC were capable of specifically homing to the fracture site and of normalizing biomechanical, histologic, and microCT parameters of healing in animals exposed to alcohol. Understanding MSC recruitment patterns and functional contributions to fracture repair may lead to their use in patients with impaired fracture healing and nonunion.

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Binge Alcohol Exposure Modulates Rodent Expression of Biomarkers of the Immunoinflammatory Response to Orthopaedic Trauma

Cited by 14 publications

References 32 publications

Systemic Inflammatory Responses and Lung Injury following Hip Fracture Surgery Increases Susceptibility to Infection in Aged Rats

Systemic Inflammatory Responses and Lung Injury following Hip Fracture Surgery Increases Susceptibility to Infection in Aged Rats

The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture

Mesenchymal Stem Cells Facilitate Fracture Repair in an Alcohol-Induced Impaired Healing Model

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