Search Results (156)

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

The aim of this work is to analyse the effectiveness of the medical use of the Cavitron Ultrasonic Surgical Aspirator (CUSA) in microsurgical treatment of Intramedullary Spinal Cord Tumors (IMSCTs), with a focus on the thermo-mechanical effects on neighbouring tissues to assess any potential damage. Indeed, CUSA emerges as an innovative solution, minimally invasive tumor excision technique, enabling controlled and focused operations. This study employs a Finite Element Analysis (FEA) to simulate the vibratory and thermal interactions occurring during CUSA application. A computational model of a vertebral column segment affected by an IMSCT was developed and analysed using ANSYS 2024 software. The simulations examined strain distribution, heat generation, and temperature propagation within the biological tissues. The FEA results demonstrate that the vibratory-induced strain remains highly localised to the application site, and thermal effects, though measurable, do not exceed the critical safety threshold of 46 °C established in the literature. These findings suggest that CUSA can be safely used within defined operational parameters, provided that energy settings and exposure times are carefully managed to mitigate excessive thermal accumulation. These conclusions contribute to the understanding of the thermo-mechanical interactions in ultrasonic tumour resection and aim to assist medical professionals in optimising surgical protocols. Full article

Spinal cord injury (SCI) is a debilitating condition that results from a culmination of acute and chronic damage to neural tissue, specifically the myelin sheath, thus impacting neurons’ abilities to synergistically perform their physiological roles. This review explores the molecular underpinnings of myelination, demyelination, and remyelination, emphasizing the role of oligodendrocyte progenitor cells (OPCs), astrocytes, and microglia in physiological, and pathophysiological, healing. Furthermore, we link these processes with emerging therapeutic strategies currently under investigation in animal and human models, underscoring areas of translational medicine that remain underutilized. The goal of this review is to provide a framework for developing more advanced interventions to restore function and improve outcomes for individuals with SCI. Full article

Amyotrophic lateral sclerosis (ALS) remains a progressive neurodegenerative disease, lacking effective causal therapies. The Wobbler mouse model harboring a spontaneous autosomal recessive mutation in the vacuolar protein sorting associated protein (Vps54), has emerged as a valuable model for investigating ALS pathophysiology and potential treatments. This model exhibits cellular and phenotypic parallels to human ALS, including protein aggregation, microglia and astrocyte activation, as well as characteristic disease progression at distinct stages. Exploring the underlying pathomechanisms and identifying therapeutic targets requires a comprehensive analysis of gene and protein expression. In this study, we examined the expression of three well-established housekeeping genes and proteins—calnexin, ß-actin, and ßIII-tubulin—in the cervical spinal cord of the Wobbler model. These candidates were selected based on their demonstrated stability across various systems like animal models or cell culture. Calnexin, an integral protein of the endoplasmic reticulum, ß-actin, a structural component of the cytoskeleton, and ß-tubulin III, a component of microtubules, were quantitatively assessed using quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression and Western blotting for protein expression. Our results revealed no significant differences in the expression of CANX, ACTB, and TUBB3 between spinal cords of wild-type and Wobbler mice at the symptomatic stage (p40) at both the gene and protein levels. These findings suggest that the pathophysiological alterations induced by the Wobbler mutation do not significantly affect the expression of these crucial housekeeping genes and proteins at p40. Overall, this study provides a basis for further investigations using the Wobbler mouse model, while highlighting the potential use of calnexin, ß-actin, and ßIII-tubulin as reliable reference genes and proteins in future research to aid in the discovery for effective therapeutic interventions. Full article

Machupo virus (MACV), a member of the Arenaviridae family and causative agent of Bolivian hemorrhagic fever, results in lethality rates of 25–35% in humans. Mice lacking the signal transducer and activator of transcription 1 (STAT-1^−/−) have previously been shown to succumb to MACV infection within 7–8 days via the intraperitoneal route. Despite these reports, we observed partial lethality in STAT-1^−/− mice following challenge with wild-type MACV. Serial sampling studies to evaluate the temporal progression of infection and pathologic changes after challenge revealed a two-phase disease course. The first phase was characterized by viral load and pathological lesions in the spleen, liver, and kidney followed by a second, lethal phase, defined by high viral titers and inflammation in the brain and spinal cord resulting in neurological manifestations and subsequent mortality. Tissue adaptation in the brains of challenged STAT-1^−/− mice resulted in a fully lethal model in STAT-1^−/− mice (mouse-adapted; maMACV). A similar two-phase disease course was observed following maMACV challenge, but more rapid dissemination of the virus to the brain and overall pathology in this region was observed. The outcome of these studies is a lethal small rodent model of MACV that recapitulates many aspects of human disease. Full article

Human induced pluripotent stem cells (iPSCs) offer immense potential as a source for cell therapy in spinal cord injury (SCI) and other diseases. The development of hypoimmunogenic, universal cells that could be transplanted to any recipient without requiring a matching donor could significantly enhance their therapeutic potential and accelerate clinical translation. To create off-the-shelf hypoimmunogenic cells, we used CRISPR-Cas9 to delete B2M (HLA class I) and CIITA (master regulator of HLA class II). Double-knockout (DKO) iPSC-derived neural progenitor cells (NPCs) evaded T-cell-mediated immune rejection in vitro and after grafting into the injured spinal cord of athymic rats and humanized mice. However, loss of HLA class I heightened susceptibility to host natural killer (NK) cell attack, limiting graft survival. To counter this negative effect, we engineered DKO NPCs to overexpress macrophage migration inhibitory factor (MIF), an NK cell checkpoint ligand. MIF expression markedly reduced NK cell-mediated cytotoxicity and improved long-term engraftment and integration of NPCs in the animal models for spinal cord injury. These findings demonstrate that MIF overexpression, combined with concurrent B2M and CIITA deletion, generates hiPSC neural derivatives that escape both T- and NK-cell surveillance. This strategy provides a scalable route to universal donor cells for regenerative therapies in SCI and potentially other disorders. Full article

Evoked potentials (EPs), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), are used to assess neural conduction in spinal cord injury (SCI) and multiple sclerosis (MS), conditions marked by demyelination, inflammation, and axonal damage. Machine learning (ML), using data-driven algorithms, enhances EPs’ prognostic utility, but evidence synthesis is limited. This meta-analysis evaluated the predictive performance of EP-based ML models for SCI recovery (ASIA scale) and MS progression (EDSS) using a random-effects model. Five studies (n = 583) were included, extracting accuracy and area under the curve (AUC). Pooled results showed high predictive accuracy of 77.7% (95% CI, 75.1–80.3%; I² = 57%) and AUC 0.82 (95% CI, 0.79–0.85; I² = 55%). Stratified analyses by disease type (SCI vs. MS) or injury severity were not feasible due to the limited number of studies (n = 5). Sensitivity analysis excluding a rat model (N = 551) showed stable results (accuracy 76.9%; AUC 0.81). SSEP latency and MEP time series were key predictors, with amplitude critical in SCI and multimodal approaches enhancing performance. Moderate heterogeneity (I² = 55–57%) and limited studies constrain generalizability. This meta-analysis highlights EPs’ prognostic potential in ML-driven precision neurology, advocating for further human studies to validate multimodal approaches. Full article

Background: Severe spinal cord injury (SCI) represents a debilitating condition with long-term physical and socioeconomic impacts. Understanding the pathophysiology of SCI and therapeutic interventions such as decompressive laminectomy and expansive duraplasty is crucial for optimizing patient outcomes. Objective: This systematic review explores the pathophysiology of SCI and evaluates evidence linking decompressive laminectomy and duraplasty to improved neuroplasticity and recovery. Methods: A comprehensive search was conducted in PubMed, Web of Science, and Cochrane Library for studies on decompressive surgery in SCI. Inclusion criteria were original articles investigating pathophysiology, neuroplasticity mechanisms, or surgical outcomes. Data on pathophysiological changes, molecular markers, and functional outcomes were extracted. Results: From 1240 initial articles, 43 studies were included, encompassing both animal models and human clinical data. Findings highlighted the role of inflammatory cascades, blood–spinal cord barrier disruption, and neurotrophic factor modulation in recovery. Decompressive duraplasty was associated with improved intrathecal pressure (ITP) management and neuroplasticity markers, such as BDNF and GAP-43. Conclusions: This review underscores the therapeutic potential of decompressive laminectomy and duraplasty in SCI. While evidence suggests benefits in promoting neuroplasticity, further research is needed to elucidate molecular mechanisms and refine interventions. Full article

Background/Objectives: The complex pathophysiology of painful cervical radiculopathy is only partially understood. Neuroimmune activation in the dorsal root ganglion and spinal cord is assumed to underlie the genesis of radicular pain. Molecular positron emission tomography (PET) using the radiotracer [¹¹C]DPA713, which targets the 18-kDa translocator protein (TSPO), offers the ability to quantify neuroinflammation in humans in vivo. The primary objectives of this study were to (1) assess whether uptake of [¹¹C]DPA713, a metric of neuroinflammation, is higher in the neuroforamina and spinal cord of patients with painful cervical radiculopathy compared with that in pain-free participants and (2) assess whether [¹¹C]DPA713 uptake is associated with clinical parameters, such as pain intensity. Methods: Dynamic 60 min [¹¹C]DPA713 PET/CT scans were acquired, and regions of interest were defined for neuroforamina and spinal cord. Resulting time-activity curves were fitted to a single-tissue compartment model using an image-derived input function, corrected for plasma-to-whole blood ratios and parent fractions, to obtain the volume of distribution (V_T) as the primary outcome measure. Secondary neuroinflammation metrics included 1T2k V_T without metabolite correction (1T2k_WB) and Logan V_T. Results: The results indicated elevated levels of 1T2k V_T at the neuroforamina (p < 0.04) but not at the spinal cord (p = 0.16). Neuroforamina and spinal cord 1T2k V_T lack associations with clinical parameters. Secondary neuroinflammatory metrics show associations with clinical parameters such as the likelihood of neuropathic pain. Conclusions: These findings enhance our understanding of painful cervical radiculopathy’s pathophysiology, emphasizing the neuroforamina levels of neuroinflammation as a potential therapeutic target. Full article

Innovations in spinal cord injury (SCI) models are crucial for developing effective therapies. This study introduces a novel in vitro SCI model using cultures of primary mixed spinal cord cells from rat pups, featuring key spinal cord cell types. This model offers distinct advantages in terms of feasibility, reproducibility, and cost-effectiveness, requiring only basic cell culture equipment. Following hyperosmotic stress via sorbitol treatment, the model recapitulated SCI pathophysiological hallmarks, with a 65% reduction in cell viability and gradual cell death over 48 h, making it ideal for evaluating neuroprotective agents. Notably, the human adipose tissue stem cell (hASC) secretome provided significant protection: it preserved metabolic viability, reduced β amyloid precursor protein (β-APP) expression in surviving neurons, and modulated the shift in the astrocytic morphotype. A transcriptomic profile of the effect of the hASC secretome treatment showed significant functional enrichments related to cell proliferation and cycle progression pathways. In addition to supporting the use of the hASC secretome as a therapy for SCI, this study is the first to use sorbitol as a hyperosmolar stressor to recapitulate key aspects of SCI pathophysiology. Thereby, this model can be used as a promising platform for evaluating therapeutic agents targeting neuroprotection and neuroregeneration, offering outputs related to cell death, neuronal stress, and protection, as well as induction of glial reactivity. Full article

Hand, Foot, and Mouth Disease (HFMD) is a viral illness caused by enterovirus infections. While the introduction of the enterovirus 71 (EV71) vaccine has significantly reduced the number of EV71-related cases, the continued spread of Coxsackievirus A16 (CVA16) remains a major public health threat. Previous studies have shown that human SCARB2 (hSCARB2) knock-in (KI) mice, generated using embryonic stem cell (ESC) technology, are susceptible to CVA16. However, these models have failed to reproduce the clinical pathology and neurotoxicity after CVA16 infection. Therefore, there is an urgent need for a more reliable and effective animal model to study CVA16. In this study, we successfully created a hSCARB2 KI mouse model targeting the ROSA26 locus using CRISPR/Cas9 gene editing technology. The application of CRISPR/Cas9 enabled stable and widespread expression of hSCARB2 in the model. After infection, the KI mice exhibited a clinical pathology that closely mimics human infection, with prominent limb weakness and paralysis. The virus was detectable in multiple major organs of the mice, with peak viral load observed on day 7 post-infection, gradually clearing thereafter. Further analysis revealed widespread neuronal necrosis and infiltration of inflammatory cells in the brain and spinal cord of the KI mice. Additionally, significant activation of astrocytes (GFAP-positive) and microglia (IBA1-positive) was observed in the brain, suggesting that CVA16 infection may induce limb paralysis by attacking neuronal cells. Overall, this model effectively replicates the neuropathological changes induced by CVA16 infection and provides a potential experimental platform for studying CVA16-associated pathogenesis and neurotoxicity. Full article

Background/Objectives: Spinal cord injury (SCI) presents significant challenges in restoring motor function, with limited therapeutic options available. Recent advancements in neuromodulation technologies, such as brain-spine interface (BSI), epidural electrical stimulation (EES), and deep brain stimulation (DBS), offer promising solutions. This review article explores the integration of these approaches, focusing on their potential to restore function in SCI patients. Findings: DBS has shown efficacy in SCI treatment with several stimulation sites identified, including the nucleus raphe magnus (NRM) and periaqueductal gray (PAG). However, transitioning from animal to human studies highlights challenges, including the technical risks of targeting the NRM in humans instead of rodent models. Additionally, several other regions have shown potential for motor rehabilitation, including the midbrain locomotor region (MLR) pathways, cuneiform nucleus (CnF), pedunculopontine nucleus (PPN), and lateral hypothalamic. DBS with EES further supports motor recovery in SCI; however, this approach requires high-DBS amplitude, serotonergic pharmacotherapy, and cortical activity decoding to attenuate stress-associated locomotion. BSI combined with EES has recently emerged as a promising novel therapy. Although human studies are limited, animal models have provided evidence supporting its potential. Despite these advancements, the effectiveness of DBS and combined systems remains limited in cases of complete central denervation. Conclusions: The integration and combination of DBS, BSI, and EES represent a transformational approach to treating and restoring function in patients with SCI. While further research is needed to optimize these strategies, these advancements hold immense potential for improving the quality of life in SCI patients and advancing the field of neuromodulation. Full article

Body stalk anomaly (BSA) is a complex congenital condition characterized by defects in the body wall, skeletal abnormalities, and an absent or abnormal umbilical cord (UC). A classification system for BSA, based on wall and skeletal abnormalities, is proposed and includes eight types observed in porcine models. These classifications consider combinations of thoracoabdominoschisis, abdominoschisis, anal atresia, genitourinary anomalies, and skeletal defects, including extreme retroflexion, scoliosis, vertebral agenesis, hemivertebrae, and thoracic or limb anomalies. While previous studies often treat limb-body wall complex (LBWC) as a separate condition, this study includes cases with co-occurring limb and spinal defects in a new classification, spinal-limb-body wall complex (SPLBWC). Additional skeletal classifications—spine-body wall complex (SPBWC), sternal-body wall complex (STBWC), and sternal-spinal-body wall complex (SSBWC)—are introduced to account for variations in structural anomalies. Nonstructural skeletal anomalies such as deformities, amputations, and arthrogryposis are excluded from the structural classifications. This comprehensive system, based on existing human and porcine models, provides a framework for the systematic categorization of BSA variations. Such an approach supports accurate diagnosis, enhances understanding of developmental defects, and improves clinical management and research outcomes in both veterinary and human medicine. Full article

Migraines are a frequently occurring neurological condition that affects up to 16% of the global population. The precise pathomechanism of the disease remains unknown, but from animal and human observations, it appears that calcium/calmodulin-dependent protein kinase II alpha (CamKIIα), pituitary adenylate cyclase-activating polypeptide (PACAP), and vasoactive intestinal polypeptide (VIP) are involved in its pathogenesis. One of the animal models of migraines uses the systemic administration of nitroglycerin (NTG), which, as a nitric oxide (NO) donor, initiates a self-amplifying process in the trigeminal system, leading to central sensitization. Endocannabinoids, such as anandamide (AEA), are thought to play a modulatory role in trigeminal activation and sensitization phenomena. In the present experiment, we aimed to investigate the effect of NTG and AEA on CamKIIα, PACAP/VIP, and vasoactive intestinal polypeptide type 1 receptor (VPAC1) expression levels in the upper cervical spinal cord (C1-C2) of rats, where trigeminal nociceptive afferents are clustered. Four groups of animals were formed: in the first group, the rats received only the vehicle; in the second group, they were treated with an intraperitoneal injection of NTG (10 mg/kg); animals in the third and fourth groups received AEA (2 × 5 mg/kg) half an hour before and one hour after the placebo or treatment with NTG. Four hours after the placebo/NTG injection, the animals were transcardially perfused, and the cervical spinal cords were removed for Western blot. Our results show that both NTG and AEA alone can increase the expression of CamKIIα and VPAC1 in the C1-C2 segments. Interestingly, the combination of NTG and AEA had no such effect on these markers, possibly due to various negative feedback mechanisms. Full article

In recent years, the increasing number of patients with spinal cord injuries, strokes, and lower limb disabilities has led to the gradual development of rehabilitation-assisted exoskeleton robots. A critical aspect of these robots is their ability to accurately sense human movement intentions to achieve smooth and natural control. This paper describes research carried out on predicting the motion angles of human lower limb joints. Based on the design of a signal acquisition system for physiological muscle signals and inertial measurement unit (IMU) data, a hybrid neural network prediction model (QRTCN-BiLSTM) and a single neural network prediction model (QRBiLSTM) were constructed using quantile regression, temporal convolution network (TCN) and bidirectional long short-term memory network (BiLSTM), respectively. At the same time, 7-channel surface electromyographic signals (sEMG) and 12-channel IMU data from hip and knee joints were collected and input into the QRBiLSTM and QRTCN-BiLSTM models to unfold the training and analyze the comparison. The results show that the QRTCN-BiLSTM model can more accurately infer human movement intention and provide a more reliable and accurate prediction tool for human–robot interaction research in rehabilitation robotics. Full article