a-novel-in-vitro-model-of-blast-traumatic-brain-injury

A Novel <em>In Vitro</em> Model of Blast Traumatic Brain Injury

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Imperial College London

Vascularity of the soft tissues around a bone fracture is critical for successful healing, particularly when the vessels in the medullary canal are ruptured. The objective of this work was to use laser Doppler and micro-computer tomography (micro-CT) scanning to characterise neovascularisation of the soft tissues surrounding the fracture during healing. Thirty-two Sprague-Dawley rats underwent mid-shaft osteotomy of the left femur, stabilised with a custom-designed external fixator. Five animals were killed at each of 2, 4 days, 1, 2, 4 and 6 weeks post-operatively. Femoral blood perfusion in the fractured and intact contralateral limbs was measured using laser Doppler scanning pre- and post-operatively and throughout the healing period. At sacrifice, the common iliac artery was cannulated and infused with silicone contrast agent. Micro-CT scans of the femur and adjacent soft tissues revealed vessel characteristics and distribution in relation to the fracture zone. Blood perfusion dropped immediately after surgery and then recovered to greater than the pre-operative level by proliferation of small vessels around the fracture zone. Multi-modal imaging allowed both longitudinal functional and detailed structural analysis of the neovascularisation process. 

Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning.

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.

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

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.

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

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.

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

The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave-induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury.

Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model.

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.

Article	Year
Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning. Medical & biological engineering & computing\| PubMed ID: 23881721	2013
Gait compensations in rats after a temporary nerve palsy quantified using temporo-spatial and kinematic parameters. Journal of neuroscience methods\| PubMed ID: 24768577	2014
Prolonged but not short-duration blast waves elicit acute inflammation in a rodent model of primary blast limb trauma. Injury\| PubMed ID: 26838938	2016
CD43Lo classical monocytes participate in the cellular immune response to isolated primary blast lung injury. The journal of trauma and acute care surgery\| PubMed ID: 27306447	2016
Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model. Journal of neurotrauma\| PubMed ID: 29285980	2018
Tibial Osteotomy as a Mechanical Model of Primary Osteoarthritis in Rats. Scientific reports\| PubMed ID: 29572481	2018

Warren Macdonald

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