The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods. In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days. Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response

Summary Statement. The mechanism of spinal cord injury varies across the human population and this may be important for the development of effective therapies. Therefore, detailed understanding of how variables such as impact velocity and depth affect cord tissue damage is important. Introduction. Studies have shown an independent effect of impact velocity and depth on injury severity, thereby suggesting importance of the interaction between the two for spinal cord injury. This work examines both the individual and interactive effects of impact velocity and impact depth on demyelination, tissue sparing, and behavioural outcomes in the rat cervical spinal cord. It also aims to understand the contribution of the energy applied during impact, not only the impact factors. Decoupling the effects of these two impact parameters will help to describe the injury mechanism. Maximum principal strain has also been shown to be useful as a predictor for neural tissue damage in vivo and in finite element (FE) models. A better understanding of this relationship with experimental results may help to elucidate the mechanics of spinal cord injury. Methods. In this study, 54 male Sprague-Dawley rats were given a contusion spinal cord injury at impact speeds of 8 mm/s, 80 mm/s, or 800 mm/s with depths of 0.9 mm or 1.5 mm. Animals recovered for 7 days followed by behavioural assessment and examination of the spinal cord tissue for demyelination and tissue sparing at 1 mm intervals, ±3 mm rostrocaudally to the epicentre. In parallel, a previously developed finite element model of the rat spinal cord was used to examine the resulting maximum principal strains in the spinal cord for correlations with histological and mechanical impact data. Results and discussion. Impact depth was a consistent factor in predicting axonal damage, tissue sparing, and the resulting behavioural deficit. Increased impact velocity resulted in significantly higher impact energies and measureable tissue damage at the 1.5 mm impact depth, but not at the 0.9 mm impact depth and is best displayed by the percentage of axon damage at the injury epicentre. Linear correlation analysis with FEA strain showed significant (p≪0.001) correlations with axonal damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with white matter (R2=0.90) and grey matter (R2=0.76) sparing. Discussion and Conclusion. The difference in injury severity to velocity at different impact depths identifies the existence of threshold interactions between the two impact factors. Beyond this point incremental increases in either velocity or depth are more likely to result in significantly increased impact energy and thus tissue damage and functional impairment. The relationship between the impact depth and velocity of injury demonstrated a more rate sensitive response to spinal cord tissue damage at the deep (1.5 mm) impact depth than at the shallow (0.9 mm) impact depth. Impact velocity also became quickly less significant than impact depth in determining tissue damage further from the epicentre. Furthermore, the results shown by this work extend the research identifying significant correlations between maximum principal strain and neurological tissue damage

Introduction and Objective. Despite the low incidence of pilon fractures among lower limb injuries, their high-impact nature presents difficulties in surgical management and recovery. Current literature includes a wide range of different management strategies, however there is no universal treatment algorithm. We aim to determine clinical outcomes in patients with open and closed pilon fractures, managed using a treatment algorithm that was applied consistently over the span of this study. Materials and Methods. This retrospective study was conducted at a single institution, including 141 pilon fractures in 135 patients, from August 2014 to January 2021. AO/OTA classification was used to classify fractures. Among closed fractures, 12 had type 43A, 18 had type 43B, 61 had type 43C. Among open fractures, 11 had type 43A, 12 had type 43B, 27 had type 43C. Open fractures were further classified with Gustilo-Anderson (GA); type 1: n=8, type 2: n=10, type 3A: n=12, type 3B: n=20. Our treatment algorithm consisted of fine wire fixator (FWF) for severely comminuted closed fractures (AO/OTA type 43C3), or open fractures with severe soft tissue injury (GA type 3). Otherwise, open reduction internal fixation (ORIF) was performed. When required, minimally invasive osteosynthesis (MIO) was performed in combination with FWF to improve joint congruency. All open fractures, and closed fractures with severe soft tissue injury (skin contusion, fracture blister, severe oedema) were initially treated with temporary ankle-spanning external fixation. For all open fracture patients, surgical debridement, soft tissue cover with a free or pedicled flap were performed. For GA types 1 and 2, this was done with ORIF in the same operating session. Those with severe soft tissue injury (GA type 3) were treated with FWF four to six weeks after soft tissue management was completed. Primary outcome was AOFAS Ankle-Hindfoot score at 3, 6 and 12-months post-treatment. Secondary outcomes include time to partial weight-bear (PWB) and full weight-bear (FWB), bone union time. All complications were recorded. Results. Mean AOFAS score 3, 6, and 12 months post-treatment for open and closed fracture patients were 44.12 and 53.99 (p=0.007), 62.38 and 67.68 (p=0.203), 78.44 and 84.06 (p=0.256), respectively. 119 of the 141 fractures healed without further intervention (84.4%). Average time to bone union was 51.46 and 36.48 weeks for open and closed fractures, respectively (p=0.019). Union took longer in closed fracture patients treated with FWF than ORIF (p=0.025). On average, open and closed fracture patients took 12.29 and 10.76 weeks to PWB (p=0.361); 24.04 and 20.31 weeks to FWB (p=0.235), respectively. Common complications for open fractures were non-union (24%), post-traumatic arthritis (16%); for closed fractures they were post-traumatic arthritis (25%), superficial infection (22%). Open fracture was a risk factor for non-union (p=0.042; OR=2.558, 95% CI 1.016–6.441), bone defect (p=0.001; OR=5.973, 95% CI 1.986–17.967), and superficial infection (p<0.001; OR=4.167, 95% CI 1.978–8.781). Conclusions. The use of a two-staged approach involving temporary external fixation followed by definitive fixation, provides a stable milieu for soft tissue recovery. FWF combined with MIO, where required for severely comminuted closed fractures, and FWF for open fractures with severe soft tissue injury, are safe methods achieving low complication rates and good functional recovery

Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the pathophysiology of SCI by altering microglial responses. The mice were anesthetized with pentobarbital (75 mg/kg i.p.) and were subjected to a contusion injury (70 kdyn) at the 10th thoracic level using an Infinite Horizons Impactor (Precision Systems Instrumentation). For flow cytometry, the samples were stained with the antibodiesand analyzed using a FACS Aria II flow cytometer and the FACSDiva software program (BD Biosciences). We retrospectively identified 528 SCI patients admitted to the Department of Orthopaedic Surgery at the Spinal Injuries Center (Fukuoka, Japan) between June 2005 and May 2011. The patients' data were obtained from their charts. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kB (NF-kB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury

Summary Statement. The spinal cord showed marked sensibility to acute compression causing complete and irreversible injury. On the contrary, the spinal cord has more ability for adaptation to slow progressive compression mechanisms having the possibility of neural recovery after compression release. Introduction. The aim of this experimental study was to establish, by means of neurophysiologic monitoring, the degree of compression needed to cause neurologic injury to the spinal cord, and analyze whether these limits are different making fast or slow compression. Material and Methods. Spinal cord was exposed from T7 to T11 in 5 domestic pigs with a mean weight of 35 kg. The T8 and T9 spinal roots were also exposed. A pair of sticks, attached to a precise compression device, was set up to both sides of the spinal cord between T8 and T9 roots. Sequentially, the sticks were approximated 0.5 mm every 2 minutes causing progressive spinal cord compression. An acute compression of the spinal cord was also reproduced by a 2.5 mm displacement of the sticks. Cord to cord motor evoked potentials were obtained with two epidural catheters, stimulating proximal to T6 and recording below the compression level, distal to T10, for each sequential approach of the sticks. Results. The mean width of the dural sac was 7.1 mm. For progressive compression, increasing latency and decreasing amplitude of the evoked potentials were observed after a mean displacement of the sticks of 3.2 ± 0.9 mm, the evoked potential finally disappearing after a mean displacement of 4.6 ± 1.2 mm. The potential returned 16.8 ± 3.2 minutes after the compression was stopped in every case. The evoked potentials immediately disappeared after an acute compression 2.5 ± 0.3 mm, without any sign of recovering after 30 minutes. Conclusion. The proposed experimental model replicates the mechanism of a spinal cord injury caused by medially displaced screws into the spinal canal, causing therefore lateral compression to the spinal cord. The spinal cord showed marked sensibility to acute compression, which caused complete and irreversible injury. On the contrary, the spinal cord has more ability for adaptation to progressive and slow compression mechanisms. From a clinical point of view, it seems mandatory to avoid maneuvers of rapid mobilization or acute, even minimal, contusions of the thoracic cord

Summary Statement. In this study, we observed that MR16-1, an interleukin-6 inhibitor, recovered phosphatidylcholine containing docosahexaenoic acid at the injury site after spinal cord injury in mice model by using imaging mass spectrometry. Introduction. The current drugs for improving motor function of the limbs lost due to spinal cord injury (SCI) are ineffective. Development of new drugs for spinal cord injury is desired. MR16-1, an interleukin-6 inhibitor, is found to be effective in improving motor function after spinal cord injury in mice model. Thus, we examined the molecular mechanism in more detail. Therefore, the purpose of this study was to analyze the molecular changes in the spinal cord of the SCI mice treated with MR16-1 using imaging mass spectrometry. Methods. All experiments were performed according to the guidelines for animal experimentation and care and use of laboratory animals established by Hamamatsu University School of Medicine (Shizuoka, Japan). We used 36 adult female C57BL/6J mice for laminectomy and contusion injury of the spinal cord that were performed at the T10 level using the Infinite Horizon Impactor (IH Impactor, 60 kdyn; Muromachi, Tokyo, Japan). Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (Chugai, Tokyo Japan) (100 µg/g body weight, MR16-1 group) or a single dose of phosphate-buffered saline (PBS) of the same volume (control group). Motor function of the hind limbs was evaluated using the Basso Mouse Scale (BMS), an open-field locomotor test in which the scores range from 0 points (scored for no ankle movement) to 9 points (scored for complete functional recovery). BMS scores were recorded at 1, 7, 14, 21, 28, 35, and 42 days after SCI. The spinal cord tissues were flash frozen and were sliced to a thickness of 8 µm using a cryostat (CM1950; Leica, Wetzler, Germany). Imaging mass spectrometry was used to visualise 12 molecular species of phosphatidylcholine (PC) from thin slices of the spinal cords obtained at 7 days post-SCI. Results. The contusive SCI immediately resulted in complete paralysis. The MR16-1–treated group showed a significant improvement in the BMS locomotor score compared with the control group at both 7 days and 42 days after SCI (1.4 vs 0.2 points and 4.0 vs 1.4 points, respectively). Phospholipids at 7 days after SCI showed unique distribution patterns. In particular, PCs containing docosahexaenoic acid (DHA) localised in the gray matter region was significantly higher in the MR16-1–treated group than in the control group, at 7 days post-SCI. Discussion. MR16-1 treatment showed to improve locomotor BMS score after 7 days of SCI compared with that observed in the control group. Spinal cord injury had induced inflammation; injury sites showed changes in the lipid content. We had previously reported that PC containing DHA mostly expressed in neuron cells decrease on injury sites. In this study, we observed that MR16-1 recovered PC containing DHA at the injury site. This may be associated with the recovery of motor function

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’).

Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.