Theofano Eftaxiopoulou

Prolonged but not short duration blast waves elicit acute inflammation in a rodent model of primary blast limb trauma

BACKGROUND Blast injuries from conventional and improvised explosive devices account for 75% of injuries from current conflicts; over 70% of injuries involve the limbs. Variable duration and magnitude of blast wave loading occurs in real-life explosions and is hypothesised to cause different injuries. While a number of in vivo models report the inflammatory response to blast injuries, the extent of this response has not been investigated with respect to the duration of the primary blast wave. The relevance is that explosions in open air are of short duration compared to those in confined spaces. METHODS Hindlimbs of adult Sprauge-Dawley rats were subjected to focal isolated primary blast waves of varying overpressure (1.8-3.65kPa) and duration (3.0-11.5ms), utilising a shock tube and purpose-built experimental rig. Rats were monitored during and after the blast. At 6 and 24h after exposure, blood, lungs, liver and muscle tissues were collected and prepared for histology and flow cytometry. RESULTS At 6h, increases in circulating neutrophils and CD43Lo/His48Hi monocytes were observed in rats subjected to longer-duration blast waves. This was accompanied by increases in circulating pro-inflammatory chemo/cytokines KC and IL-6. No changes were observed with shorter-duration blast waves irrespective of overpressure. In all cases, no histological damage was observed in muscle, lung or liver. By 24h post-blast, all inflammatory parameters had normalised. CONCLUSIONS We report the development of a rodent model of primary blast limb trauma that is the first to highlight an important role played by blast wave duration and magnitude in initiating acute inflammatory response following limb injury in the absence of limb fracture or penetrating trauma. The combined biological and mechanical method developed can be used to further understand the complex effects of blast waves in a range of different tissues and organs in vivo.

Gait compensations in rats after a temporary nerve palsy quantified using temporo-spatial and kinematic parameters

BACKGROUND The aim of this work was to test a method for measuring the gait of rats with sufficient sensitivity to detect subtle locomotor changes due to pathology, injury and recovery. METHOD The gait of female Sprague-Dawley rats was assessed using an optical motion tracking system and the DigiGait™ imaging system during normal locomotion, shortly after temporary nerve block to the left hind limb and after full recovery. RESULTS The effect of low treadmill speeds (10-30 cm/s) was initially investigated. Significant changes were detected in the spatiotemporal gait parameters, consistent with those previously reported. The overall ranges of motion in the hip, knee and ankle joints were 37.5° (±7.1°), 50.2° (±9.4°) and 61.6° (±9.1°) and did not appear to change with speed, indicating that for low speed variations, kinematic comparisons across speeds may be possible. Following the induction of a temporary sciatic nerve block, the range of motion of the left ankle and knee during swing decreased by 23° and 33°, respectively (p<0.05). A compensatory change of a greater range of motion at the hip was noted in the contralateral limb (p<0.01). 90 min post injection, most of the gait parameters had returned to normal, however, minor walking deficits were still present. COMPARISON WITH EXISTING METHOD(S) Discriminant analysis showed that a combination of dynamic and kinematic parameters provides a more robust method for the classification of gait changes. CONCLUSIONS This more detailed method, employing both dynamic analysis and joint kinematics simultaneously, was found to be a reliable approach for the quantification of gait in rats.

The effect of digitisation of the humeral epicondyles on quantifying elbow kinematics during cricket bowling

Abstract In the sport of cricket the objective of the “no-ball” law is to allow no performance advantage through elbow extension during ball delivery. However, recently it has been shown that even bowlers with actions that are considered within the law show some elbow extension. The objective of this study was to investigate: [1] the effect of elbow orientation during anatomical landmark digitisation and [2] the choice of upper arm tracking cluster on the measurement of elbow angles during cricket bowling. We compared the mean elbow angles for four different elbow postures; with the joint flexed at approximately 130°, 90°, in full extension and with the elbow flexed with the humerus internally rotated, and two upper arm clusters in two different situations: [1] during a controlled movement of pure flexion-extension and [2] during cricket bowling. The digitised postures of the anatomical landmarks where the elbow was extended and at 90° of flexion were more repeatable than the other two postures. The recommendation of this study when analysing cricket bowling is to digitise the humeral epicondyles with the joint flexed at 90°, or in full extension, and to relate their positions to an upper arm cluster fixed close to the elbow.

A performance comparison between cricket bat designs

Seven cricket bats, four standard and three significantly different designs, were tested for a set of mechanical properties: equivalent bending stiffness, moment of inertia, and freely-suspended vibration. These properties are known to be related to the performance of the cricket bats in terms of pick up weight, vibrations imparted to the batsman, and energy imparted to the cricket ball. The aim of this work was to determine whether these novel designs improve the bat’s performance parameters. Intuitively correctly, results showed that by redistributing the mass of the bat further away from the rotational axis the moment of inertia increases. This results in an increase of the ball’s rebound speed after collision. Carbon fibres inserted in the handle of the bat were found to improve its vibrational performance and provide the advantage of having a stiffer blade combined with a relatively less-stiff handle, which is an optimum for imparting maximum energy to the ball.

Assessment of performance parameters of a series of five ‘historical’ cricket bat designs:

The performance of five different bat designs, from different eras spanning from 1905 to 2013, was assessed to address the question whether the changes in bat design over the years have resulted in a performance advantage to the batsman. Moment of inertia and ‘freely suspended’ vibration analysis tests were conducted, as these physical properties have been directly associated with rebound characteristics of the bats. Results showed that changes in the blade’s profile such as distribution of the blade’s weight along the edges and closer to the toe have resulted in a clear performance advantage of the newest bats in comparison with older designs. These results add to the weight of evidence in cricket that the game has changed to the benefit of the batsman and additional changes to bat design are conceivable as modern engineering tools are applied to further optimise performance.

CD43Lo classical monocytes participate in the cellular immune response to isolated primary blast lung injury.

BACKGROUND Understanding of the cellular immune response to primary blast lung injury (PBLI) is limited, with only the neutrophil response well documented. Moreover, its impact on the immune response in distal organs remains poorly understood. In this study, a rodent model of isolated primary blast injury was used to investigate the acute cellular immune response to isolated PBLI in the circulation and lung, including the monocyte response, and investigate distal subacute immune effects in the spleen and liver 6 hours after injury. METHODS Rats were subjected to a shock wave (~135 kPa overpressure, 2 ms duration) inducing PBLI or sham procedure. Rat physiology was monitored, and at 1, 3, and 6 hours thereafter, blood, lung, and bronchoalveolar lavage fluid (BALF) were collected and analyzed by flow cytometry, enzyme-linked immunosorbent assay, and histologic examination. In addition, at 6 hours, spleen and liver were collected and analyzed by flow cytometry. RESULTS Lung histology confirmed pulmonary barotrauma and inflammation. This was associated with rises in CXCL-1, interleukin 6 (IL-6), tumor necrosis factor &agr; and albumin protein in the BALF. Significant acute increases in blood and lung neutrophils and CD43Lo/His48Hi (classical) monocytes/macrophages were detected. No significant changes were seen in blood or lung “nonclassical” monocyte and in natural killler, B, or T cells. In the BALF, significant increases were seen in neutrophils, CD43Lo monocyte-macrophages and monocyte chemoattractant protein-1. Significant increases in CD43Lo and Hi monocyte-macrophages were detected in the spleen at 6 hours. CONCLUSION This study reveals a robust and selective response of CD43Lo/His48Hi (classical) monocytes, in addition to neutrophils, in blood and lung tissue following PBLI. An increase in monocyte-macrophages was also observed in the spleen at 6 hours. This profile of immune cells in the blood and BALF could present a new research tool for translational studies seeking to monitor, assess, or attenuate the immune response in blast-injured patients.

Tibial Osteotomy as a Mechanical Model of Primary Osteoarthritis in Rats

This study has presented the first purely biomechanical surgical model of osteoarthritis (OA) in rats, which could be more representative of the human primary disease than intra-articular techniques published previously. A surgical tibial osteotomy (TO) was used to induce degenerative cartilage changes in the medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the medial knee compartment of the operated animals was evaluated histologically and through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX-II). In-vivo biomechanical analyses were carried out using a musculoskeletal model of the rat hindlimb to evaluate the loading conditions in the knee pre and post-surgically. Qualitative and quantitative medial cartilage degeneration consistent with OA was found in the knees of the operated animals alongside elevated CTX-II levels and increased tibial compressive loading. The potential avoidance of joint inflammation post-surgically, the maintenance of internal joint biomechanics and the ability to quantify the alterations in joint loading should make this model of OA a better candidate for modeling primary forms of the disease in humans.

Physical Models: Organ Models for Primary Blast

With primary blast, when a shock wave hits the body, some of the energy is reflected and some absorbed by the body. As tissue within the body possesses both elastic and viscous properties (as well as some organs being multi-phasic in nature), their reactions to blast loading is complicated and difficult to predict. Different parts of the body, specifically organs, react differently to impulsive loading. This is due to a combination of their unique structure, which responds in a certain way to a mechanical stimulus, as well as the unique stress-strain state experienced in that part of the body, due to a given blast wave profile and the support conditions of that organ. This can lead to local injury development within a given organ resulting in consequences to the system as a whole (e.g. inflammation) or with damage mechanisms being interwoven and superposing. Multiple injury sites generate increased burden on the system leading to added complications in their treatment. Although in-vivo blast models continue to dominate the existing literature, these models tend to analyse whole body responses and sometimes fail to identify physical injury at the tissue level. Isolated organ experiments, termed ex-vivo models, maintain the architecture and functionality of the tissue for a short period of time and constitute a close representation of the in-vivo state [1]. This section focusses on the work assessing primary blast evaluation of the body at an organ level.

In-Vivo Models of Blast Injury

Over the years several in-vivo injury models have been developed to study the effects of blast injuries to experimental animals, in order to identify the injury mechanisms involved in the pathobiology of blast injury. This review provides an overview of the most commonly used blast injury models and the local and systemic changes induced in a wide range of tissues following blast.