Physics-informed neural network for acoustic resonance analysis in a one-dimensional acoustic tube.

This study devised a physics-informed neural network (PINN) framework to solve the wave equation for acoustic resonance analysis. The proposed analytical model, ResoNet, minimizes the loss function for periodic solutions and conventional PINN loss functions, thereby effectively using the function approximation capability of neural networks while performing resonance analysis. Additionally, it can be easily applied to inverse problems. The resonance in a one-dimensional acoustic tube, and the effectiveness of the proposed method was validated through the forward and inverse analyses of the wave equation with energy-loss terms. In the forward analysis, the applicability of PINN to the resonance problem was evaluated via comparison with the finite-difference method. The inverse analysis, which included identifying the energy loss term in the wave equation and design optimization of the acoustic tube, was performed with good accuracy.

Temporal dynamics of gait function in acute cervical spinal cord injury.

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Changing trends in traumatic spinal cord injury in an aging society: Epidemiology of 1152 cases over 15 years from a single center in Japan.

Traumatic spinal cord injury (TSCI) causes an insult to the central nervous system, often resulting in devastating temporary or permanent neurological impairment and disability, which places a substantial financial burden on the health-care system. This study aimed to clarify the up-to-date epidemiology and demographics of patients with TSCI treated at the largest SCI center in Japan. Data on all patients admitted to the Spinal Injuries Center with TSCI between May 2005 and December 2021 were prospectively collected using a customized, locally designed SCI database named the Japan Single Center Study for Spinal Cord Injury Database (JSSCI-DB). A total of 1152 patients were identified from the database. The study period was divided into the four- or five-year periods of 2005-2009, 2010-2013, 2014-2017, and 2018-2021 to facilitate the observation of general trends over time. Our results revealed a statistically significant increasing trend in age at injury. Since 2014, the average age of injury has increased to exceed 60 years. The most frequent spinal level affected by the injury was high cervical (C1-C4: 45.8%), followed by low cervical (C5-C8: 26.4%). Incomplete tetraplegia was the most common cause or etiology category of TSCI, accounting for 48.4% of cases. As the number of injuries among the elderly has increased, the injury mechanisms have shifted from high-fall trauma and traffic accidents to falls on level surfaces and downstairs. Incomplete tetraplegia in the elderly due to upper cervical TSCI has also increased over time. The percentage of injured patients with an etiology linked to alcohol use ranged from 13.2% (2005-2008) to 19% (2014-2017). Given that Japan has one of the highest aging populations in the world, epidemiological studies in this country will be very helpful in determining health insurance and medical costs and deciding strategies for the prevention and treatment of TSCI in future aging populations worldwide.

Halo vest fixation effectively maintains cervical alignment through intraoperative repositioning in patients with cervical spine instability.

Introduction: The objective of this study was to examine if halo vest fixation provides sufficient stabilization of cervical spine alignment to endorse its use through intraoperative positional changes in patients with cervical spine instability. Methods: The subjects of this study were 14 patients with cervical spine instability who were immobilized in halo vests until they underwent subsequent internal fixation surgery. After induction of anesthesia, the patients in halo vests were repositioned from the supine position to the prone position. The halo ring was fixed to the surgical table and the dorsal struts and vest were removed for surgery. Radiographs obtained in the preoperative sitting position and intraoperative prone position were compared for the following measures of cervical alignment: O-C2 angle, C2-C6 angle, pharyngeal inlet angle (PIA), atlantodental interval (ADI), Redlund-Johnell (R-J) value as a measure of O-C2 length, O-C6 length, and O-C2 length/O-C6 length (%). Results: There were no significant differences in O-C2 angle, C2-C6 angle, PIA, ADI, or O-C2 length/O-C6 length (%). However, the R-J value and O-C6 length were significantly higher in the intraoperative prone position than in the preoperative sitting position. None of the patients presented with any complications, including dysphagia or neurological deterioration. Conclusions: Our results suggest that when patients are repositioned to the prone position while immobilized in halo vests, the cervical spine is distracted in the cephalocaudal direction across all cervical segments but the cervical alignment is sufficiently maintained. Halo vests are a highly effective external fixation method for patients with cervical spine instability, allowing for a safe repositioning to the prone position for surgery while preserving cervical alignment and preventing neurological deterioration.

Verification of the Accuracy of Cervical Spinal Cord Injury Prognosis Prediction Using Clinical Data-Based Artificial Neural Networks.

BACKGROUND: In patients with cervical spinal cord injury (SCI), we need to make accurate prognostic predictions in the acute phase for more effective rehabilitation. We hypothesized that a multivariate prognosis would be useful for patients with cervical SCI. METHODS: We made two predictive models using Multiple Linear Regression (MLR) and Artificial Neural Networks (ANNs). We adopted MLR as a conventional predictive model. Both models were created using the same 20 clinical parameters of the acute phase data at the time of admission. The prediction results were classified by the ASIA Impairment Scale. The training data consisted of 60 cases, and prognosis prediction was performed for 20 future cases (test cohort). All patients were treated in the Spinal Injuries Center (SIC) in Fukuoka, Japan. RESULTS: A total of 16 out of 20 cases were predictable. The correct answer rate of MLR was 31.3%, while the rate of ANNs was 75.0% (number of correct answers: 12). CONCLUSION: We were able to predict the prognosis of patients with cervical SCI from acute clinical data using ANNs. Performing effective rehabilitation based on this prediction will improve the patient's quality of life after discharge. Although there is room for improvement, ANNs are useful as a prognostic tool for patients with cervical SCI.

Intraoperative Radiation Exposure from O-arm-based 3D Navigation in Spine Surgery.

Introduction: Intraoperative three-dimensional (3D) imaging guide technology, such as the O-arm surgical imaging system, is a beneficial tool in spinal surgery that provides real-time 3D images of a patient's spine. This study aims to determine the exposure dose from intraoperative O-arm imaging. Methods: A consecutive retrospective review of all patients undergoing spinal surgery was conducted between June 2019 and August 2022. Demographic and operative data were collected from electronic medical records. Results: Intraoperative O-arm imaging was conducted in 206 (12.9%) of 1599 patients, ranging from one to 4 scans per patient (1.17±0.43 scans). Single O-arm imaging enabled navigation of seven vertebrae in the cervical spine, seven in the thoracic spine, five in the thoracolumbar spine, and four in the lumbar spine on average. The number of O-arm shots per surgery was 1.15±0.36, 1.06±0.24, 1.61±0.7, and 1.07±0.25 for cervical, thoracic, thoracolumbar, and lumbar spinal cases, respectively. The exposure doses represented by dose length products in single O-arm imaging were 377±19 mGy-cm, 243±22 mGy-cm, 378±38 mGy-cm, and 258±11 mGy-cm for cervical, thoracic, thoracolumbar, and lumbar spine cases, respectively. We observed a weak positive correlation between the number of fused spinal levels and the exposure dose. Conclusions: Intraoperative radiation exposure from O-arm imaging was lower than the national diagnostic reference levels in Japan established based on the International Commission on Radiological Protection publication, demonstrating its safety from the standpoint of radiological protection in most cases. In surgeries with a large range of fixations, such as corrective deformity surgery, the number of imaging sessions and the amount of intraoperative radiation exposure would increase, leading surgeons to pay attention to the risk of radiation in spinal surgery.

Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.

Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.

Predicting the Progression of Spasticity in the Early Phase of Spinal Cord Injury: A Prospective Cohort Study.

Spasticity-defined as involuntary movements caused by insult to upper motor neurons after spinal cord injury (SCI)-interferes with patients' activities of daily living. Spasticity is generally identified and managed in the chronic phase of SCI, but few reports have examined the onset of spasticity after injury. The purpose of this study is to elucidate serial changes in spasticity after SCI and clarify the timing of severe spasticity. We prospectively examined individuals with acute traumatic SCI admitted within two weeks after injury. Severity of spasticity was evaluated using the Modified Ashworth Scale (MAS) at 2, 4, 6, and 8 weeks, followed by 3, 4, 5, and 6 months after injury. After completing evaluation of the cohort, the patients were divided into two groups: a spasticity group with MAS scores ≥3 (marked increase in muscle tone through most of the range of motion (ROM)) in at least one joint movement within 6 months of injury and a control group with MAS scores ≤2 in all joint movements throughout the 6 months after injury. Neurological findings such as the American Spinal Injury Association (ASIA) Impairment Scale grades and ASIA motor scores were also assessed at all time points, and the correlations between the onset of spasticity, severity of spasticity, and neurological findings were analyzed. There were 175 patients with traumatic SCI who were assessed consecutively for 6 months after injury. The MAS scores of the group significantly increased over time until 4 months after injury. The spasticity group had significantly higher MAS scores compared with the control group as early as 2 weeks post-injury. We found that the patients with earlier onset of spasticity had higher final MAS scores. No correlation was found between the ASIA Impairment Scale grade and the onset of spasticity. Our results reveal that the development of severe spasticity may be predictable from as early as 2 weeks after SCI, suggesting that early therapeutic intervention to mitigate problematic spasticity may enhance the benefits of post-injury rehabilitation.

Human Spinal Oligodendrogenic Neural Progenitor Cells Enhance Pathophysiological Outcomes and Functional Recovery in a Clinically Relevant Cervical Spinal Cord Injury Rat Model.

Traumatic spinal cord injury (SCI) results in the loss of neurons, oligodendrocytes, and astrocytes. Present interventions for SCI include decompressive surgery, anti-inflammatory therapies, and rehabilitation programs. Nonetheless, these approaches do not offer regenerative solutions to replace the lost cells, fiber tracts, and circuits. Neural stem/progenitor cell (NPC) transplantation is a promising strategy that aims to encourage regeneration. However, NPC differentiation remains inconsistent, thus, contributing to suboptimal functional recovery. As such, we have previously engineered oligodendrogenically biased NPCs (oNPCs) and demonstrated their efficacy in a thoracic model of SCI. Since the majority of patients with SCI experience cervical injuries, our objective in the current study was to generate human induced pluripotent stem cell-derived oNPCs (hiPSC-oNPCs) and to characterize these cells in vitro and in vivo, utilizing a clinically relevant rodent model of cervical SCI. Following transplantation, the oNPCs engrafted, migrated to the rostral and caudal regions of the lesion, and demonstrated preferential differentiation toward oligodendrocytes. Histopathological evaluations revealed that oNPC transplantation facilitated tissue preservation while diminishing astrogliosis. Moreover, oNPC transplantation fostered remyelination of the spared tissue. Functional analyses indicated improved forelimb grip strength, gait, and locomotor function in the oNPC-transplanted rats. Importantly, oNPC transplantation did not exacerbate neuropathic pain or induce tumor formation. In conclusion, these findings underscore the therapeutic potential of oNPCs in promoting functional recovery and histopathological improvements in cervical SCI. This evidence warrants further investigation to optimize and advance this promising cell-based therapeutic approach.

Time Course and Characteristics of the Nutritional Conditions in Acute Traumatic Cervical Spinal Cord Injury.

Introduction: This retrospective cohort study aimed to examine the nutritional time course and elucidate the critical period of undernutrition following acute traumatic cervical spinal cord injury (CSCI). Methods: The study was performed at a single facility that treated spinal cord injuries. We examined individuals with acute traumatic CSCI admitted to our hospital within 3 days of injury. Both prognostic nutritional index (PNI) and controlling nutritional status (CONUT) scores, which objectively reflect nutritional and immunological conditions, were assessed at admission and 1, 2, and 3 months after the injury. The American Spinal Injury Association impairment scale (AIS) categorizations and severity of dysphagia were evaluated at these time points. Results: A total of 106 patients with CSCI were evaluated consecutively for 3 months after injury. Individuals with AIS categorizations of A, B, or C at 3 days after injury were significantly more undernourished than those with an AIS categorization of D at 3 months after injury, indicating that individuals with mild paresis better maintained their nutritional condition after injury. Nutritional conditions, as assessed by both PNI and CONUT scores, improved significantly between 1 and 2 months after injury, whereas no significant differences were found between admission and 1 month after injury. Nutritional status and dysphagia were significantly correlated at each time point (p<0.001), indicating that swallowing dysfunction is an important factor associated with malnutrition. Conclusions: Nutritional conditions showed significant gradual improvements from 1 month after the injury. We must pay attention to undernutrition, which is associated with dysphagia, especially in individuals with severe paralysis during the acute phase following injury.

Significance of the neurological level of injury as a prognostic predictor for motor complete cervical spinal cord injury patients.

Objective: To investigate the usefulness of the combination of neurological findings and magnetic resonance imaging (MRI) as a prognostic predictor in patients with motor complete cervical spinal cord injury (CSCI) in the acute phase.Design: A cross-sectional analysisSetting: Department of Orthopaedic Surgery, Spinal Injuries CenterParticipants/Methods: Forty-two patients with an initial diagnosis of motor complete CSCI (AIS A, n = 29; AIS B, n = 13) within 72 h after injury were classified into the recovery group (Group R) and the non-recovery group (Group N), based on the presence or absence of motor recovery (conversion from AIS A/B to C/D) at three months after injury, respectively. The Neurological Level of Injury (NLI) at the initial diagnosis was investigated and the presumptive primary injured segment of the spinal cord was inferred from MRI performed at the initial diagnosis. We investigated whether or not the difference between the presumptive primary injured segment and the NLI exceeded one segment. The presence of a difference between the presumptive primary injured segment and the NLI was compared between Groups R and N.Results: The number of cases with the differences between the presumptive primary injured segment and the NLI was significantly higher in Group N than in Group R.Conclusion: The presence of differences between the presumptive primary injured segment and the NLI might be a poor improving prognostic predictor for motor complete CSCI. The NLI may be useful for predicting the recovery potential of patients with motor complete CSCI when combined with the MRI findings.

Incidence and risk factors of pneumonia following acute traumatic cervical spinal cord Injury.

OBJECTIVES: To elucidate the incidence and risk factors for pneumonia after acute traumatic cervical spinal cord injury (CSCI). DESIGN: Retrospective cohort study.Setting: Spinal injuries center in Japan.Participants: Of 184 individuals who were admitted within 2 weeks after acute traumatic cervical spinal injuries, 167 individuals who met the criteria were included in this study.Interventions: The occurrence of pneumonia, degree of dysphagia using the Dysphagia Severity Scale, patient age, history of smoking, presence of tracheostomy, vital capacity, level of injury, and the American Spinal Injury Association Impairment Scale (AIS) 2 weeks after injury were assessed.Outcomes: Incidence of pneumonia were analyzed. Moreover, the risk factors of pneumonia were evaluated using logistic regression analysis. RESULTS: From the 167 individuals who met the criteria, 30 individuals (18%) had pneumonia; in 26 (87%) of these individuals, pneumonia was aspiration related, defined as Dysphagia Severity Scale ≤ 4. The median occurrence of aspiration pneumonia was 11.5 days after injury. A logistic regression analysis revealed that severe AIS and severe Dysphagia Severity Scale scores were significant risk factors of pneumonia after CSCI. CONCLUSIONS: It was highly likely that the pneumonias following CSCI were related to aspiration based on the Dysphagia Severity Scale. In addition, most of the patients developed aspiration pneumonia within 1 month after injury. Aspiration and severe paralysis were significant risk factors for pneumonia. The treatment of dysphagia in the acute phase should be considered an important indicator to prevent pneumonia.

Diaphragm pacing implantation in Japan for a patient with cervical spinal cord injury: A case report.

RATIONALE: Traumatic cervical spinal cord injury (SCI) is a devastating condition leading to respiratory failure that requires permanent mechanical ventilation, which is the main driver of increased medical costs. There is a great demand for establishing therapeutic interventions to treat respiratory dysfunction following severe cervical SCI. PATIENT CONCERNS AND DIAGNOSIS: We present a 24-year-old man who sustained a cervical displaced C2-C3 fracture with SCI due to a traffic accident. As the patient presented with tetraplegia and difficulty in spontaneous breathing following injury, he was immediately intubated and placed on a ventilator with cervical external fixation by halo orthosis. The patient then underwent open reduction and posterior fusion of the cervical spine 3 weeks after injury. Although the patient showed significant motor recovery of the upper and lower limbs over time, only a slight improvement in lung capacity was observed. INTERVENTIONS AND OUTCOMES: At 1.5 years after injury, a diaphragmatic pacing stimulator was surgically implanted to support the patient's respiratory function. The mechanical ventilator support was successfully withdrawn from the patient 14 weeks after implantation. We observed that both the vital capacity and tidal volume of the patient were significantly promoted following implantation. The patient finally returned to daily life without any mechanical support. LESSONS: The findings of this report suggest that diaphragmatic pacing implantation could be a promising treatment for improving respiratory function after severe cervical SCI. To our knowledge, this is the first SCI patient treated with a diaphragm pacing implantation covered by official medical insurance in Japan.

Species-specific debromination of BDE99 in teleost fish: The relationship between debromination ability and bioaccumulation patterns of PBDEs.

Polybrominated diphenyl ethers (PBDEs) are known to be broken down by debromination reactions in the natural environment, such as by photolysis, microbial and metabolic processes. Although species-specific debromination of PBDEs by fish has also been reported, it has only rarely been studied from the phylogenetic perspective. The objective of this study is to reveal the factors affecting species-specific debromination through validation between the bioaccumulation of PBDEs in muscle tissue and the ability to debrominate BDE99. As environmental observations, PBDE concentrations in muscle tissues were analyzed in 25 wild fish (Cyprinidae, Gobiidae and others). As in vitro experiments, debromination experiments were conducted using the hepatic microsomes of 21 fish species. Significant amounts of BDE99 were detected in almost none of the Cyprinidae. A relatively higher debromination ability was confirmed in the Cyprinidae in in vitro experiments. The Cyprinidae thus appears to be a family with high debromination ability. BDE99 has been detected in some goby species but not others. This pattern was also seen in in vitro experiments, suggesting that debromination ability is not consistent within the Gobiidae. In further quantitative comparisons, kinetic parameters such as Km and vmax were determined for selected fish species. The common carp (Cyprinus carpio) and the Japanese crucian carp (Carassius cuvieri), both Cyprinidae, showed higher vmax values, whereas vmax values among three Gobiidae diverged widely. A comparison of field observations and in vitro experiments, revealed the bioaccumulation ratio of BDE99 to be affected by the BDE99 debromination ability of each fish species. This is the first report on classification of BDE99 accumulation ratio by debromination ability and a phylogenetic species comparison based on kinetic parameters for debromination reactions of PBDEs by fish.

Long-term outcomes of spinal meningioma resection with outer layer of dura preservation technique.

Spinal meningioma is a common benign intradural spinal tumor. It has been reported that the local recurrence rate after surgical resection increases with longer follow-up duration. Simpson grade 1 resection could reduce the risk of recurrence, but this procedure needs dural reconstruction, which would cause cerebrospinal fluid (CSF) leakage or iatrogenic spinal cord injury. Saito et al. reported dura preservation technique to reduce the risk of CSF leakage, in which the meningioma together with the inner layer of the dura is removed and the outer layer is preserved for simple dural closure. The long-term outcomes with this technique have never been investigated. In this study, we retrospectively analyzed the data of 38 surgically treated patients (dura preservation technique, 12 patients; Simpson grade 2 resection, 26 patients) to assess the long-term recurrence rate (mean, 121.5 months; range, 60-228 months). The local recurrence rate in the dura preservation group was 8.3% (1 of 12 cases), which was similar to that in Simpson grade 2 resection group (2 of 26 cases [7.7%]). Although this case series did not indicate the significant difference in the recurrence rates between the dura preservation group and Simpson grade 2 group, we consider that this technique still has advantages for surgically less invasiveness in terms of dural reconstruction which is necessary for Simpson grade 1 and higher possibility of complete resection of tumors compared with Simpson grade 2 resection.

Acute spinal subdural hematoma: A case report of spontaneous recovery from paraplegia.

RATIONALE: Spontaneous spinal subdural hematoma (SSDH) is a rare disease that can cause severe permanent neurological dysfunction. Here we present a case of spontaneous SSDH, in which a series of magnetic resonance images (MRIs) taken through the course of the disease facilitated understanding of the resolution process of the hematoma and the diagnosis of SSDH. PATIENT CONCERNS: A 59-year-old male presented with sudden severe back pain and rapid onset of paraplegia. This symptom had continued developing while he was transferred to the emergency department. Initial physical examination showed flaccid paralysis of both lower limbs with areflexia and loss of all sensation below T6 bilaterally. MRI images showed an anterior subdural hematoma from C7 to T7 with spinal cord compression. DIAGNOSIS: Based on MRI findings, the diagnosis was SSDH. INTERVENTIONS: We chose conservative treatment of 1-week bed rest and intensive rehabilitation for the patient due to the presence of sacral sparing and the slight motor recovery at 24 hours after the onset. OUTCOMES: Frequent MRI images demonstrated that the spinal cord compression was surprisingly mitigated only 2 days and mostly absorbed 4 days after the onset. The patient's motor function was recovered completely and he was discharged after 8 weeks of hospitalization. LESSONS: Our chronological MRI findings provide crucial information for diagnosing SSDH and also suggest that spinal surgeons should consider the potential option of a conservative approach for treating SSDH. Although prompt selection of a therapeutic strategy for SSDH could be challenging, the surgeons could observe the course of the patient's neurological status for a few days to detect signs of spontaneous recovery.

The beneficial aspects of spasticity in relation to ambulatory ability in mice with spinal cord injury.

STUDY DESIGN: Experimental study with mice. OBJECTIVES: Spasticity is a common complication after spinal cord injury (SCI) and has detrimental aspects, such as persistent pain and involuntary muscle spasms. This study aimed to assess the influence of antispastic therapy on locomotor function after SCI. SETTING: University-based laboratory in Fukuoka, Japan. METHODS: A mouse model of spasticity was developed by producing incomplete SCI at the 9th thoracic level. At 8 weeks after SCI, an antispastic drug, baclofen, was intraperitoneally administered to six injured and two sham-operated mice. The severity of spasticity was evaluated by the modified Ashworth scoring (MAS) system, and locomotor function was evaluated by the Basso-Beattie-Bresnahan (BBB) scale/Basso mouse score (BMS). RESULTS: The administration of baclofen significantly improved spasticity in the SCI mice and the mean MAS decreased to from 6.2 to 2.8. However, at the same time, it significantly exacerbated the locomotor dysfunction of the SCI mice and the mean BMS decreased from 4.7 to 2.3. The time-course of the changes in locomotor function coincided with the time-course of the spasticity score. We also confirmed that the administration of baclofen was not associated with any changes in either locomotor function or spasticity of the sham-operated control mice. CONCLUSIONS: Our results suggest that spasticity has a certain beneficial effect on ambulation ability. It is important to note that antispastic treatments may be associated with a risk of impairing the preserved function of chronic SCI patients.

Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds.

Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an "ailment not to be treated" into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope that a cure for SCI was on the horizon. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. However, recent advances in SCI research have greatly increased our understanding of the fundamental processes underlying SCI and fostered increasing optimism that these multiple treatment strategies are finally coming together to bring about a new era in which we will be able to propose encouraging therapies that will lead to appreciable improvements in SCI patients. In this review, we outline the pathophysiology of SCI that makes the spinal cord refractory to regeneration and discuss the research that has been done with cell replacement and biomaterial implantation strategies, both by itself and as a combined treatment. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI.

Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

Progression of local kyphosis after conservative treatment for compressive cervical spine fracture with spinal cord injury.

INTRODUCTION: Compressive-flexion type cervical spine fracture is typically accompanied by apparent dislocation of the facet joints, undesirable cervical alignment, and devastating neurological dysfunction, which provides strong rationale for rendering prompt operative treatment. However, the validity of conservative treatment for compressive-flexion cervical spine injury in cases with preserved congruity of the facet joints has yet to be elucidated. The purpose of this study is to evaluate the long-term outcome of cervical alignment following conservative treatment for compressive-flexion cervical spine injury with preserved congruity of the facet joints. METHODS: A total of 662 patients who experienced spinal cord injury from 2007 to 2017 were included and underwent retrospective review in a single institute. Thirteen patients were identified as receiving conservative therapy following compressive-flexion cervical spine fractures with spinal cord injury. Clinical and radiological results were collected, including vertical fractures of the vertebral column, laminar fractures, progression of local kyphosis, and neurological status. The degree of the local cervical kyphosis was evaluated with two methods: the posterior tangent method and the endplate method. RESULTS: All 13 patients were male, and the mean age at the time of injury was 28.4 years. The mean follow-up period was 3 years. Although none of the patients presented neurological deterioration after the injury, the degree of local kyphosis was increased at the time of final follow-up compared to what was observed at the time of injury. Patient age at the time of injury and concurrent vertical fracture of vertebral body could have been influencing factors for the progression of the kyphosis. While laminar fracture affected the kyphosis at the time of injury, it was not a strong influencing factor of the overall progression of local kyphosis. CONCLUSIONS: The conservative option for the compressive-flexion cervical injury allowed us to treat without exacerbating neurological symptoms as long as the facet joints are preserved. However, in terms of cervical alignment, surgical stabilization may have been desirable for these patients. Notably, the younger patients and the patients with vertical fracture of the cervical vertebral column in this type of injury required closer observation to help prevent the progression of local kyphosis.