Journal of neurotrauma最新文献

{"title":"Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury.","authors":"Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy","doi":"10.1089/neu.2024.0233","DOIUrl":"10.1089/neu.2024.0233","url":null,"abstract":"<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"212-228"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic Resonance Imaging Parameters in the Subacute Phase after Traumatic Cervical Spinal Cord Injury: A Prospective, Observational Longitudinal Study. Part 1: Conventional Imaging Characteristics.","authors":"Lukas Grassner, Iris Leister, Florian Högel, Ludwig Sanktjohanser, Matthias Vogel, Orpheus Mach, Doris Maier, Andreas Grillhösl","doi":"10.1089/neu.2023.0592","DOIUrl":"10.1089/neu.2023.0592","url":null,"abstract":"<p><p>Magnetic resonance imaging (MRI) remains the gold standard for evaluating spinal cord tissue damage after spinal cord injury (SCI). Several MRI findings may have some prognostic potential, but their evolution over time, especially from the subacute to the chronic phase has not been studied extensively. We performed a prospective observational longitudinal study exploring the evolution of MRI parameters from the subacute to chronic phase after human traumatic cervical SCI. The study, conducted between 2016 and 2021, involved standardized neurological examinations and MRI scans 1 month, 3 months, and 1 year after SCI. The study cohort comprises 52 patients with cervical SCI. Patients were classified into AIS grades (American Spinal Injury Association Impairment Scale), and neurological recovery was assessed using the Integrated Neurological Change Score. The MRI protocol included various routine sequences, allowing the evaluation of established parameters such as intramedullary hemorrhage, lesion dimensions, maximum spinal cord compression, and various grading scales. The persistence of intramedullary hemorrhage one month after injury was associated with worse lower extremity motor scores and pinprick values after 3 months, and also in the chronic phase. In addition, dorsal column T2-weighted hyperintensities detected 3 months post-injury and in the chronic phase were related to lower pinprick sensory scores. The basic score and Sagittal Grade at 1 month were predictive for motor function 3 months after SCI and for neurological recovery between 1 and 3 months after injury. The study contributes valuable insights into the utility of routine MRI sequences for evaluating traumatic cervical SCI during the subacute to chronic phase. The identified MRI parameters and scores offer prognostic information and could support clinical decision-making.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"307-315"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Measurement of Pressure Within the Spinal Cord to Optimize Spinal Cord Perfusion Pressure Using a Porcine Model of Spinal Cord Injury.","authors":"Femke Streijger, Aysha Allard Brown, Lukas Grassner, Kyoung-Tae Kim, Michael Rizzuto, Kitty So, Neda Manouchehri, Megan Webster, Shera Fisk, Mypinder Sekhon, Donald Griesdale, Brian Kwon","doi":"10.1089/neu.2024.0308","DOIUrl":"10.1089/neu.2024.0308","url":null,"abstract":"<p><p>Recent studies have reported that monitoring spinal cord perfusion pressure (SCPP) using a pressure probe to measure \"intraspinal pressure\" (ISP) within the subdural space at the injury site may improve the hemodynamic management of acute spinal cord injury (SCI) patients. This study aimed to investigate, within a pig model of SCI, the relationship between the ISP measured within the subdural space and the \"spinal cord pressure\" (SCP) measured within the spinal cord itself. Specifically, we sought to characterize the changes to ISP and SCP over time, both rostral and caudal to the injury epicenter, and in relation to native spinal cord morphometry. Female Yucatan mini-pigs were subjected to a T10 contusion-compression injury. Pressure probes were inserted inside the spinal cord parenchyma for SCP and within the subdural space for ISP, 5-mm rostral, and caudal from the injury site. SCP and ISP were then measured over an 8-hour period post-SCI. Ultrasound images were taken before and after SCI to monitor changes in spinal cord morphometry in the early hours post-injury. Spinal cord swelling was observed in all cases; however, only half of the animals exhibited increased SCP and ISP rostrally. In these, a gradient across the injury site was observed in the ISP measured rostrally and caudally when swelling of the spinal cord filled the subdural space, and the cord was seen to be abutting against the dura. The remaining animals showed a negligible increase in ISP and SCP (<+1 mmHg). The variation in pressure response was influenced heavily by the size of the subdural space surrounding the cord. In cases where we could establish an \"optimal SCPP\" based on the autoregulatory function of the spinal cord, a discernible variance of approximately 10 mmHg was detected between the values derived from ISP versus SCP. These results suggest that changes in ISP and SCP after SCI are influenced by native spinal cord morphometry and that the location of measurement is important to consider, particularly in situations where the swelling of the injured cord results in an occlusion of the cerebrospinal fluid (CSF) flow through the subdural space.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":"42 3-4","pages":"165-181"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Real-World Clinical Practice in Time to Surgery Following Thoracolumbar Spinal Cord Injury: An Observational Study of North American Trauma Centers from 2010 to 2020.","authors":"Ahmad Essa, Armaan K Malhotra, Husain Shakil, Jetan Badhiwala, Avery B Nathens, Eva Y Yuan, Yingshi He, Andrew S Jack, Francois Mathieu, Jefferson R Wilson, Christopher D Witiw","doi":"10.1089/neu.2024.0125","DOIUrl":"10.1089/neu.2024.0125","url":null,"abstract":"<p><p>This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. Descriptive plots and a multivariable Poisson regression model with time to spine surgery as the primary outcome were constructed. This study included 4350 adult patients with complete SCI surgically treated across 449 trauma centers. Within this group, 3978 (91.4%) patients were diagnosed with thoracic SCI and 372 (8.6%) patients were diagnosed with lumbar SCI. The overall mean time to surgery was 31.6 h (±34.1). Early surgery (≤24 h) was performed in 2599 patients (59.7%). An estimated annual reduction of 1.6 h in time to surgery was demonstrated over the study period, starting initially at a mean of 47.6 h (±40.6) in 2010, and reaching a mean of 25.3 h (±30) in 2020. Multivariable Poisson regression adjusting for patient, injury, and institution confounders, demonstrated a significant decrease in time to surgery by 5% per year over the study period (incidence rate ratios [IRR] = 0.95, 95% confidence interval [CI]: 0.93-0.96). Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"262-271"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal Cord Blood Perfusion Deficit is Associated with Clinical Impairment after Spinal Cord Injury.","authors":"Anna Lebret, Sabina Frese, Simon Lévy, Armin Curt, Virginie Callot, Patrick Freund, Maryam Seif","doi":"10.1089/neu.2024.0267","DOIUrl":"10.1089/neu.2024.0267","url":null,"abstract":"<p><p>Spinal cord injury (SCI) results in intramedullary microvasculature disruption and blood perfusion deficit at and remote from the injury site. However, the relationship between remote vascular impairment and functional recovery remains understudied. We characterized perfusion impairment <i>in vivo</i>, rostral to the injury, using magnetic resonance imaging (MRI), and investigated its association with lesion extent and impairment following SCI. Twenty-one patients with chronic cervical SCI and 39 healthy controls (HC) underwent a high-resolution MRI protocol, including intravoxel incoherent motion (IVIM) and T2*-weighted MRI covering C1-C3 cervical levels, as well as T2-weighted MRI to determine lesion volumes. IVIM matrices (i.e., blood volume fraction, velocity, flow indices, and diffusion) and cord structural characteristics were calculated to assess perfusion changes and cervical cord atrophy, respectively. Patients with SCI additionally underwent a standard clinical examination protocol to assess functional impairment. Correlation analysis was used to investigate associations between IVIM parameters with lesion volume and sensorimotor dysfunction. Cervical cord white and gray matter were atrophied (27.60% and 21.10%, <i>p</i> < 0.0001, respectively) above the cervical cord injury, accompanied by a lower blood volume fraction (-22.05%, <i>p</i> < 0.001) and a higher blood velocity-related index (+38.72%, <i>p</i> < 0.0001) in patients with SCI compared with HC. Crucially, gray matter remote perfusion deficit correlated with larger lesion volumes and clinical impairment. This study shows clinically eloquent perfusion deficit rostral to a SCI, its magnitude driven by injury severity. These findings indicate trauma-induced widespread microvascular alterations beyond the injury site. Perfusion MRI matrices in the spinal cord hold promise as biomarkers for monitoring treatment effects and dynamic changes in microvasculature integrity following SCI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"280-291"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Hemodynamic Management Using Norepinephrine on Cardiorespiratory Function Following Cervical Spinal Cord Contusion in Rats.","authors":"Rui-Yi Chen, Kun-Ze Lee","doi":"10.1089/neu.2024.0342","DOIUrl":"10.1089/neu.2024.0342","url":null,"abstract":"<p><p>Cervical spinal cord injury usually leads to cardiorespiratory dysfunction due to interruptions of the supraspinal pathways innervating the phrenic motoneurons and thoracic sympathetic preganglionic neurons. Although clinical guidelines recommend maintaining the mean arterial pressure within 85-90 mmHg during the first week of injury, there is no pre-clinical evidence from animal models to prove the therapeutic efficacy of hemodynamic management. Accordingly, the present study was designed to investigate the therapeutic efficacy of hemodynamic management in rats with cervical spinal cord contusion. Adult male rats underwent cervical spinal cord contusion and the implantation of osmotic pumps filled with saline or norepinephrine (NE) (125 μg/(kg·h) for 1 week). The cardiorespiratory function of unanesthetized rats was examined using a non-invasive blood pressure analyzer and double-chamber plethysmography. Cervical spinal cord contusion caused a long-term reduction in the mean arterial pressure and tidal volume. This hypotensive response was significantly reversed in contused rats receiving NE (1 day: 88 ± 19 mmHg; 2 weeks: 96 ± 13 mmHg) compared with contused rats receiving saline (1 day: 72 ± 15 mmHg; 2 weeks: 82 ± 10 mmHg). NE also significantly improved the tidal volume 1 day post-injury (contused + NE: 0.7 ± 0.2 mL; contused + saline: 0.5 ± 0.1 mL). Immunofluorescence staining results revealed that injury-induced reductions of noradrenergic and glutamatergic fibers within the thoracic spinal cord were significantly improved by NE. These results provided the evidence demonstrating that hemodynamic management using NE significantly improves cardiorespiratory function by alleviating neural pathway damage after cervical spinal cord contusion.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"197-211"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.","authors":"Gregory J R States, Trevor Clark, Darlene A Burke, Alice Shum-Siu, David S K Magnuson","doi":"10.1089/neu.2023.0640","DOIUrl":"10.1089/neu.2023.0640","url":null,"abstract":"<p><p>Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"316-332"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Lipid Metabolism in the Injured Mouse Spinal Cord.","authors":"Natalie E Scholpa, Epiphani C Simmons, Justin M Snider, Kelsey Barrett, Lauren G Buss, Rick G Schnellmann","doi":"10.1089/neu.2024.0385","DOIUrl":"10.1089/neu.2024.0385","url":null,"abstract":"<p><p>Following spinal cord injury (SCI), there is a short-lived recovery phase that ultimately plateaus. Understanding changes within the spinal cord over time may facilitate targeted approaches to prevent and/or reverse this plateau and allow for continued recovery. Untargeted metabolomics revealed distinct metabolic profiles within the injured cord during recovery (7 days postinjury [DPI]) and plateau (21 DPI) periods in a mouse model of severe contusion SCI. Alterations in lipid metabolites, particularly those involved in phospholipid (PL) metabolism, largely contributed to overall differences. PLs are hydrolyzed by phospholipases A2 (PLA2s), yielding lysophospholipids (LPLs) and fatty acids (FAs). PL metabolites decreased between 7 and 21 DPI, whereas LPLs increased at 21 DPI, suggesting amplified PL metabolism during the plateau phase. Expression of various PLA2s also differed between the two time points, further supporting dysregulation of PL metabolism during the two phases of injury. FAs, which can promote inflammation, mitochondrial dysfunction, and neuronal damage, were increased regardless of time point. Carnitine can bind with FAs to form acylcarnitines, lessening FA-induced toxicity. In contrast to FAs, carnitine and acylcarnitines were increased at 7 DPI, but decreased at 21 DPI, suggesting a loss of carnitine-mediated mitigation of FA toxicity at the later time point, which may contribute to the cessation of recovery post-SCI. Alterations in oxidative phosphorylation and tricarboxylic acid cycle metabolites were also observed, indicating persistent although dissimilar disruptions in mitochondrial function. These data aid in increasing our understanding of lipid metabolism following SCI and have the potential to lead to new biomarkers and/or therapeutic strategies.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"182-196"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Proteomic and Bioinformatic Analysis of Human Spinal Cord Injury Plasma Identifies Proteins Associated with the Complement Cascade and Liver Function as Potential Prognostic Indicators of Neurological Outcome.","authors":"Gabriel Mateus Bernardo Harrington, Paul Cool, Charlotte Hulme, Jessica Fisher-Stokes, Mandy Peffers, Wagih El Masri, Aheed Osman, Joy Roy Chowdhury, Naveen Kumar, Srinivasa Budithi, Karina Wright","doi":"10.1089/neu.2023.0064","DOIUrl":"10.1089/neu.2023.0064","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Spinal cord injury (SCI) is a major cause of disability, with complications postinjury often leading to lifelong health issues with the need for extensive treatment. Neurological outcome post-SCI can be variable and difficult to predict, particularly in incompletely injured patients. The identification of specific SCI biomarkers in blood may be able to improve prognostics in the field. This study has utilized proteomic and bioinformatic methodologies to investigate differentially expressed proteins in plasma samples across human SCI cohorts with the aim of identifying candidate prognostic biomarkers and biological pathway alterations that relate to neurological outcome. Blood samples were taken, following informed consent, from American Spinal Injury Association impairment scale (AIS) grade C \"improvers\" (those who experienced an AIS grade improvement) and \"nonimprovers\" (no AIS change) and AIS grade A and D at &lt;2 weeks (\"acute\") and ∼3 months (\"subacute\") postinjury. The total protein concentration from each sample was extracted, with pooled samples being labeled and nonpooled samples treated with ProteoMiner&lt;sup&gt;™&lt;/sup&gt; beads. Samples were then analyzed using two 4-plex isobaric tag for relative and absolute quantification (iTRAQ) analyses and a label-free experiment for comparison before quantifying with mass spectrometry. Data are available via ProteomeXchange with identifiers PXD035025 and PXD035072 for the iTRAQ and label-free experiments, respectively. Proteomic datasets were analyzed using OpenMS (version 2.6.0). R (version 4.1.4) and, in particular, the R packages MSstats (version 4.0.1) and pathview (version 1.32.0) were used for downstream analysis. Proteins of interest identified from this analysis were further validated by enzyme-linked immunosorbent assay. The data demonstrated proteomic differences between the cohorts, with the results from the iTRAQ approach supporting those of the label-free analysis. A total of 79 and 87 differentially abundant proteins across AIS and longitudinal groups were identified from the iTRAQ and label-free analyses, respectively. Alpha-2-macroglobulin, retinol-binding protein 4 (RBP4), serum amyloid A1, peroxiredoxin 2 (PRX-2), apolipoprotein A1, and several immunoglobulins were identified as biologically relevant and differentially abundant, with potential as individual candidate prognostic biomarkers of neurological outcome. Bioinformatics analyses revealed that the majority of differentially abundant proteins were components of the complement cascade and most interacted directly with the liver. Many of the proteins of interest identified using proteomics were detected only in a single group and therefore have potential as binary (present or absent) biomarkers, RBP4 and PRX-2 in particular. Additional investigations into the chronology of these proteins and their levels in other tissues (cerebrospinal fluid in particular) are needed to better understand the underlying pathophysiology, including","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"292-306"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Feasibility of Early Activity-Based Therapy Following Severe Traumatic Spinal Cord Injury: Results from a Single-Arm Pilot Trial.","authors":"Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong","doi":"10.1089/neu.2024.0297","DOIUrl":"10.1089/neu.2024.0297","url":null,"abstract":"<p><p>Early activity-based therapy (E-ABT) has the potential to decrease complications and radically improve neurofunctional recovery following traumatic spinal cord injury (TSCI). Unfortunately, E-ABT after TSCI has never been attempted in humans due to practical obstacles and potential safety concerns. This study aims to report on the safety and feasibility outcomes of the Protocol for Rapid Onset of Mobilization in Patients with Traumatic SCI (PROMPT-SCI) trial: the first-ever trial of E-ABT in critically ill patients who suffered a severe TSCI. To do so, 45 patients with severe TSCI were recruited to participate in the PROMPT-SCI trial between April 2021 and August 2023. The intervention consisted of daily 30-min sessions of motor-assisted in-bed leg cycling for 14 days, starting within 48 h of early surgery (≈72 h from the initial trauma). Adverse events were closely monitored, and completion rates were evaluated. Out of the 45 participants, 36 (80%) completed a full and safe session within 48 h of surgery and all participants managed to achieve this outcome within 72 h of surgery. Over the full 14-day protocol, the average completion rate of sessions was 87.2 ± 22.7% (range: 7.1-100.0%). A total of three patients were mechanically ventilated during the protocol and all three had 100% completion of sessions. Frequent reasons for unattempted/incomplete sessions were scheduling conflicts with activities related to care (e.g., bronchoscopy) and fatigue/uncontrolled pain before initiating cycling. We also report no neurological deterioration caused by cycling and no major adverse event recorded during or between sessions. In conclusion, this study suggests that E-ABT can be safely initiated within 48-72 h after a severe TSCI with no major adverse event. In the form of daily passive in-bed leg cycling, E-ABT is also acceptable for target users, and feasible over the course of the first weeks after the initial trauma, as shown by our excellent rate of completed sessions (87%). The present results also suggest that improved collaboration with intensive care unit staff, including intensivists and nurses, could improve these rates even further.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"242-249"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}