Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury.

The immune system plays critical roles in promoting tissue repair during recovery from neurotrauma but is also responsible for unchecked inflammation that causes neuronal cell death, systemic stress, and lethal immunodepression. Understanding the immune response to neurotrauma is an urgent priority, yet current models of traumatic brain injury (TBI) inadequately recapitulate the human immune response. Here, we report the first description of a humanized model of TBI and show that TBI places significant stress on the bone marrow.

A Novel Platelet Function Assay for Trauma.

Background: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients.

A Useful Device to Measure Kinetics of Platelet Contraction.

Platelet contraction provides a minimally invasive source for physiologic information. In this article, we describe a device that directly measures the kinetics of platelet contraction. Whole blood is injected between acrylic plates and an adherent clot forms.

Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E (PGE ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells.

3D Printed Surgical Instruments: The Design and Fabrication Process.

Background: 3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments.

Bone marrow-derived stromal cell therapy for traumatic brain injury is neuroprotective via stimulation of non-neurologic organ systems.

Bone marrow-derived mesenchymal stromal cells (MSCs) used as "MSC therapy" after traumatic brain injury act as remote "bioreactors" via stimulation of lung macrophages and augmention of T regulatory cell production by the spleen, leading to systemic increases in circulating anti-inflammatory cytokines and alteration of the locoregional milieu of the central nervous system. The altered intracerebral microenvironment leads to modulation of the resident microglia population, thereby stimulating an increase in the ratio of M2 (anti-inflammatory) macrophage to M1 (proinflammatory) macrophage, and it is this effect that accounts for the observed neuroprotection.

Effects of nonocclusive mesenteric hypertension on intestinal function: implications for gastroschisis-related intestinal dysfunction.

Introduction: Infants with gastroschisis (GS) have significant morbidity from dysmotility, feeding intolerance, and are at increased risk of developing intestinal failure. Although the molecular mechanisms regulating GS-related intestinal dysfunction (GRID) are largely unknown, we hypothesized that mechanical constriction (nonocclusive mesenteric hypertension (NMH)) from the abdominal wall defect acts as a stimulus for GRID. The purpose of this study was to determine the effect of NMH on intestinal function and inflammation.

A novel mechanism for neutrophil priming in trauma: potential role of peritoneal fluid.

Background: We sought to determine the effect of peritoneal fluid from a novel animal model of abdominal compartment syndrome (ACS) on the proinflammatory status of polymorphonuclear leukocytes (PMNs) and monocytes. We hypothesize that peritoneal fluid is a potential priming and/or activating agent for PMNs/monocytes.

Methods: ACS was induced in female Yorkshire swine, and peritoneal fluid was collected at the time of decompressive laparotomy.

A novel physiologic model for the study of abdominal compartment syndrome (ACS).

Background: : Current abdominal compartment syndrome (ACS) models rely on intraperitoneal instillation of fluid, air, and other space-occupying substances. Although this allows for the study of the effects of increased abdominal pressure, it poorly mimics its pathogenesis. We have developed the first reported large animal model of ACS incorporating hemorrhagic shock/resuscitation.

Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

Background: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema.

Effect of needle diameter and flow rate on rat and human mesenchymal stromal cell characterization and viability.

Introduction: Current mesenchymal stromal cell (MSC) delivery methods require infusion/implantation through needles and/or catheters. Little investigation into the effect of delivery via catheter injection has been completed. We hypothesize that injection of rat and human MSCs through various clinically relevant-sized catheters and flow rates will not affect cell viability, characterization, or function.

Advances in progenitor cell therapy using scaffolding constructs for central nervous system injury.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation.

Regional differences in cerebral edema after traumatic brain injury identified by impedance analysis.

Objective: Cerebral edema is a common and potentially devastating sequel of traumatic brain injury. We developed and validated a system capable of tissue impedance analysis, which was found to correlate with cerebral edema.

Methods: Constant sinusoidal current (50 microA), at frequencies from 500 to 5000 Hz, was applied across a bipolar electrode unit superficially placed in a rat brain after traumatic brain injury.

Bioimpedance analysis: a guide to simple design and implementation.

Background: Bioimpedance analysis has found utility in many fields of medical research, yet instrumentation can be expensive and/or complicated to build. Advancements in electronic component design and equipment allow for simple bioimpedance analysis using equipment now commonly found in an engineering lab, combined with a few components exclusive to impedance analysis.

Materials And Methods: A modified Howland bridge circuit was designed on a small circuit board with connections for power and bioimpedance probes.