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  • Journal article
    Koziakova M, Harris K, Edge C, Franks N, White I, Dickinson Ret al., 2019,

    Noble gas neuroprotection: Xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms

    , British Journal of Anaesthesia, Vol: 123, Pages: 601-609, ISSN: 1471-6771

    BackgroundNoble gases may provide novel treatments for neurological injuries such as ischaemic and traumatic brain injury. Few studies have evaluated the complete series of noble gases under identical conditions in the same model.MethodsWe used an in vitro model of hypoxia–ischaemia to evaluate the neuroprotective properties of the series of noble gases, helium, neon, argon, krypton, and xenon. Organotypic hippocampal brain slices from mice were subjected to oxygen-glucose deprivation, and injury was quantified using propidium iodide fluorescence.ResultsBoth xenon and argon were equally effective neuroprotectants, with 0.5 atm of xenon or argon reducing injury by 96% (P<0.0001), whereas helium, neon, and krypton were devoid of any protective effect. Neuroprotection by xenon, but not argon, was reversed by elevated glycine.ConclusionsXenon and argon are equally effective as neuroprotectants against hypoxia–ischaemia in vitro, with both gases preventing injury development. Although xenon's neuroprotective effect may be mediated by inhibition of the N-methyl-d-aspartate receptor at the glycine site, argon acts via a different mechanism. These findings may have important implications for their clinical use as neuroprotectants.

  • Conference paper
    Campos-Pires R, Mohamed-Ali N, Balaet M, Aldhoun J, Abelleira-Hervas L, Aitken P, Edge C, Franks N, Dickinson Ret al., 2019,

    Xenon prevents early neuronal loss and neuroinflammation in a rat model of traumatic brain injury

    , BJA Research Forum / Anaesthetic Research Society, Publisher: Elsevier, Pages: e508-e509, ISSN: 0007-0912
  • Conference paper
    Campos-Pires R, Hirnet T, Valeo F, Ong BE, Radyushkin K, Aldhoun J, Saville J, Edge CJ, Franks NP, Thal SC, Dickinson Ret al., 2019,


    , 37th Annual National Neurotrauma Symposium, Publisher: MARY ANN LIEBERT, INC, Pages: A47-A47, ISSN: 0897-7151
  • Conference paper
    Campos-Pires R, Mohamed-Ali N, Balaet M, Aldhoun J, Abelleira-Hervas L, Aitken P, Edge CJ, Franks NP, Dickinson Ret al., 2019,


    , 37th Annual National Neurotrauma Symposium, Publisher: MARY ANN LIEBERT, INC, Pages: A116-A116, ISSN: 0897-7151
  • Conference paper
    Campos-Pires R, Yonis A, Pau A, Macdonald W, Harris K, Franks N, Edge C, Dickinson Ret al., 2019,

    Delayed xenon treatment prevents injury development following blast-neurotrauma in vitro

    , 37th Annual National Neurotrauma Symposium, Publisher: Mary Ann Liebert, Pages: A40-A41, ISSN: 0897-7151
  • Journal article
    Campos-Pires R, Hirnet T, Valeo F, Ong BE, Radyushkin K, Aldhoun J, Saville J, Edge CJ, Franks NP, Thal SC, Dickinson Ret al., 2019,

    Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

    , British Journal of Anaesthesia, Vol: 123, Pages: 60-73, ISSN: 0007-0912
  • Conference paper
    Campos-Pires R, Hirnet T, Valeo F, Ong BE, Saville J, Radyushkin K, Edge C, Franks N, Thal S, Dickinson Ret al., 2019,

    Xenon Treatment Prevents Late Onset Cognitive Impairment and Improves Survival Following Traumatic Brain Injury in Mice

    , 13th World Conference on Brain Injury, Pages: 220-220, ISSN: 0269-9052
  • Conference paper
    Campos-Pires R, Mohamed-Ali N, Balaet M, Aldhoun J, Abelleira-Hervas L, Aitken P, Edge C, Franks N, Dickinson Ret al., 2019,

    Xenon Treatment Reduces Secondary Injury Development and Prevents Neuronal Loss and Microglial Proliferation in a Rat Model of Traumatic Brain Injury

    , 13th World Conference on Brain injury, Pages: 222-222, ISSN: 0269-9052
  • Conference paper
    Campos-Pires R, Yonis A, Pau A, Macdonald W, Harris K, Edge C, Franks N, Dickinson Ret al., 2019,

    The Noble Gas Xenon Prevents Injury Development Following Blast-Traumatic Brain Injury In Vitro

    , 13th World Conference on Brain Injury, Pages: 218-218, ISSN: 0269-9052
  • Journal article
    Grigoriadis G, Carpanen D, Webster CE, Ramasamy A, Newell N, Masouros SDet al., 2019,

    Lower limb posture affects the mechanism of injury in under-body blast

    , Annals of Biomedical Engineering, Vol: 47, Pages: 306-316, ISSN: 0090-6964

    Over 80% of wounded Service Members sustain at least one extremity injury. The 'deck-slap' foot, a product of the vehicle's floor rising rapidly when attacked by a mine to injure the limb, has been a signature injury in recent conflicts. Given the frequency and severity of these combat-related extremity injuries, they require the greatest utilisation of resources for treatment, and have caused the greatest number of disabled soldiers during recent conflicts. Most research efforts focus on occupants seated with both tibia-to-femur and tibia-to-foot angles set at 90°; it is unknown whether results obtained from these tests are applicable when alternative seated postures are adopted. To investigate this, lower limbs from anthropometric testing devices (ATDs) and post mortem human subjects (PMHSs) were loaded in three different seated postures using an under-body blast injury simulator. Using metrics that are commonly used for assessing injury, such as the axial force and the revised tibia index, the lower limb of ATDs were found to be insensitive to posture variations while the injuries sustained by the PMHS lower limbs differed in type and severity between postures. This suggests that the mechanism of injury depends on the posture and that this cannot be captured by the current injury criteria. Therefore, great care should be taken when interpreting and extrapolating results, especially in vehicle qualification tests, when postures other than the 90°-90° are of interest.

  • Journal article
    Campos Pires R, Yonis A, Macdonald W, Harris K, Edge C, Mahoney P, Dickinson Ret al., 2018,

    A novel In vitro model of blast traumatic brain injury

    , Jove-Journal of Visualized Experiments, Vol: 142, ISSN: 1940-087X

    Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

  • Journal article
    Logan N, Camman M, Williams G, Higgins Cet al., 2018,

    Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model

    , BONE, Vol: 117, Pages: 149-160, ISSN: 8756-3282

    Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified cell culture model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and significantly accelerated cell mineralisation. Reduced representation bisulfite sequencing revealed that the shock wave altered methylation of gene promoters, leading to opposing changes in gene expression. Using a drug to target ITGAV, whose expression was perturbed by the shock wave, we found that we could abrogate the deposition of mineral in our model. These findings show how new therapeutics for the treatment of heterotopic ossification can be identified using cell culture models.

  • Journal article
    Rosenberg N, Bull AMJ, 2018,

    Application of a mechanobiological algorithm to investigate mechanical mediation of heterotopic bone in trans-femoral amputees

    , Scientific Reports, Vol: 8, ISSN: 2045-2322

    Heterotopic ossification (HO) is the process of bone formation in tissues that are not usually osseous. It occurs in 60% of those with blast-related amputations. HO can result in reduced range of motion, pain, nerve impingement and can affect prosthesis fitting and is caused by a combination of mechanical, biological, local and systemic factors. As with normal bone formation and remodelling, it is expected that heterotopic bone responds to mechanical stimuli and understanding this relationship can give insight into the pathology. The objective of this research was to investigate whether a physiological 2D computational model that considers both mechanical and biological factors can be used to simulate HO in the residual limb of a trans-femoral amputee. The study found that characteristic morphologies of HO were reproduced by adjusting the loading environment. Significant effects were produced by changing the loading direction on the femur; this is potentially associated with different initial surgical interventions such as muscle myodesis. Also, initial treatment such as negative pressure through a dressing was found to change the shape of heterotopic bone.

  • Journal article
    Webster CE, Clasper J, Stinner DJ, Eliahoo J, Masouros SDet al., 2018,

    Characterization of Lower Extremity Blast Injury

    , MILITARY MEDICINE, Vol: 183, Pages: E448-E453, ISSN: 0026-4075
  • Conference paper
    Campos-Pires R, Armstrong S, Sebastiani A, Luh C, Gruss M, Radyushkin K, Hirnet T, Werner C, Engelhard K, Franks NP, Thal SC, Dickinson Ret al., 2018,

    Xenon treatment improves short-term and long-term outcomes in a rodent model of traumatic brain injury

    , British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e21-e21, ISSN: 0007-0912
  • Conference paper
    Campos-Pires R, Yonis A, Pau A, Macdonald W, Harris K, Edge CJ, Franks NP, Mahoney PF, Dickinson Ret al., 2018,

    Xenon is neuroprotective against blast traumatic brain injury in vitro

    , British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e23-e23, ISSN: 0007-0912
  • Journal article
    Newell N, Pearce AP, Spurrier E, Gibb I, Webster CE, Masouros SD, Clasper JCet al., 2018,

    Analysis of isolated transverse process fractures sustained during blast related events

    , Journal of Trauma and Acute Care Surgery, Vol: 85, Pages: S129-S133, ISSN: 2163-0763

    BACKGROUND: A range of devastating blast injuries have been sustained by personnel during recent conflicts. Previous studies have focused on severe injuries, including to the spine, however, no study has specifically focused on the most common spinal injury; transverse process (TP) fractures. Although their treatment usually requires limited intervention, analysis of TP fractures may help determine injury mechanisms. METHODS: Data was collected from victims with spinal fractures injured in Improvised Explosive Device (IED) attacks, from the UK's Joint Theatre Trauma Registry. The level and side of each TP fracture was recorded, as well as associated injuries, whether they were mounted or dismounted, and outcome (survivor or fatality). RESULTS: The majority of TP fractures were lumbar (80%). More bilateral (both left and right fractures at the same level), and L5 TP fractures, were seen in fatalities than survivors. In the mounted group, lumbar TP fractures were statistically significantly associated with fatality, head injury, non-compressible torso haemorrhage, pelvic injury, and other spinal injuries. In the dismounted group, thoracic TP fractures were associated with head, chest wall, and other spinal injuries, and lumbar TP fractures were associated with pelvic, and other spinal injuries. CONCLUSIONS: Different injury mechanisms of the TP in the mounted and dismounted groups are likely. Inertial forces acting within the torso due to rapid loading being transferred through the seat, or high intra-abdominal pressures causing the tensile forces acting through the lumbar fascia to avulse the TPs are likely mechanisms in the mounted group. Blunt trauma, violent lateral flexion-extension forces, or rapid flail of the lower extremities causing tension of the psoas muscle, avulsing the TP are likely causes in the dismounted group. Isolated lumbar TP fractures can be used as markers for more severe injuries, and fatality, in mounted blast casualties. LEVEL OF EVIDENCE: P

  • Journal article
    Zaharie DZ, Phillips ATM,

    Pelvic construct prediction of trabecular and cortical bone structural architecture

    , Journal of Biomechanical Engineering, ISSN: 0148-0731
  • Journal article
    Campos Pires R, Koziakova M, Yonis A, Pau A, Macdonald W, Harris K, Edge C, Franks N, Mahoney P, Dickinson Ret al., 2018,

    Xenon protects against blast-induced traumatic brain injury in an in vitro model

    , Journal of Neurotrauma, Vol: 35, Pages: 1037-1044, ISSN: 0897-7151

    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.

  • Conference paper
    Forte AE, Etard OE, Reichenbach JDT, 2018,

    Selective Auditory Attention At The Brainstem Level

    , ARO 2018

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