Discovery of a Novel Yadav-Kunal Reflex in Context of Upper Motor Neuron Lesions: A Report of Three Cases.

Introduction: Numerous reflexive responses have been documented as alterations to the Babinski sign within upper motor neuron lesions. However, scant attention has been given to reflexes beyond these, which exhibit independence from the extensor plantar response. These reflexes predominantly form polysynaptic arcs, with nociceptive stimuli acting as afferents. Case Report: The reflex was serendipitously discovered in an 18-year-old female patient who presented with spastic paraplegia with bowel and bladder involvement, as a consequence of an aneurysmal bone cyst of the D3 (dorsal) vertebrae, and the same was named after the authors as "Yadav-Kunal reflex" which can be defined as: "In individuals with spastic paraparesis, forcibly plantarflexing the toes will result in sudden jerky flexion of the knee and hip on the same side." This novel reflex was further investigated and validated in two additional patients with spastic paraplegia: one, a 45-year-old female with D9-D10 Pott's spine and bowel and bladder involvement, and the other, a 65-year-old male with D10-D11 compressive myelopathy and bowel and bladder involvement. This reflex was meticulously tracked until the abatement of spasticity following surgical intervention. Notably, its manifestation was evident in individuals experiencing spastic paraparesis, dissipating concomitantly with the resolution of spasticity - a direct clinical correlation. Conversely, the reflex was conspicuously absent in cases of flaccid paraplegia. Conclusion: Spasticity, characterized by an increase in muscle tone on swift stretching movements, is a manifestation of a stretch reflex disorder. This condition is primarily induced by lesions affecting upper motor neurons. The activation of muscle spindles in toe dorsiflexors (primarily governed by the L5 nerve) occurs during forceful elongation caused by plantarflexion.

3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury.

Spinal cord injury (SCI) could cause permanent impairment to motor or sensory functions. Pre-cultured neural stem cell (NSC) hydrogel scaffolds were demonstrated to be a promising approach to treat SCI with anti-inflammatory effect, axon regrowth and motor function restore. Here in this study, we performed coaxial extrusion process to fabricate a core-shell hydrogel microfiber with high NSC density in the core portion. Oxidized hyaluronic acid (OHA), carboxymethyl chitosan (CMC) and Matrigel blend was used as matrix for NSC growth and to facilitate the fabrication process. During in vitro differentiation culture, it is found that NSC microfiber could differentiate into neuron and astrocyte with higher efficiency compared with NSC cultured in petri dishes. Furthermore, during in vivo transplantation, NSC microfibers were coated with poly lactic acid (PLA) nanosheet by electrospinning for reinforcement. The coated NSC nanofibers showed higher anti-inflammatory effect and lesion cavity filling rate compared with control group. Meanwhile, more neuron- and oligodendrocyte-like cells were visualized in lesion epicenter. Finally, axon regrowth across the whole lesion site was observed, demonstrating the microfiber could guide renascent axon regrowth. Experiment results indicate that the NSC microfiber is a promising bioactive treatment for complete SCI treatment with better outcomes. .

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Acute non-traffic traumatic spinal cord injury in the aging population: Analysis of the National Inpatient Sample 2005-2018.

BACKGROUND: This study aimed to determine risk factors for poor in-hospital outcomes in a large cohort of older adult patients with acute non-traffic traumatic spinal cord injury (tSCI). METHODS: This is a population-based, retrospective, observational study. Data of older adults ≥65 years with a primary discharge diagnosis of acute non-traffic tSCI were extracted from the US National Inpatient Sample (NIS) database 2005-2018. Traffic-related tSCI admissions or patients lacking complete data on age, sex and outcomes of interest were excluded. Univariate and multivariate logistic regression analysis was used to determine associations between variables and in-hospital outcomes. RESULTS: Data of 49,449 older patients (representing 246,939 persons in the US) were analyzed. The mean age was 79.9 years. Multivariable analyses revealed that severe International Classification of Disease (ICD)-based injury severity score (ICISS) (adjusted odds ratio [aOR] = 3.14, 95% confidence interval [CI]: 2.77-3.57), quadriplegia (aOR = 2.79, 95%CI: 2.34-3.32), paraplegia (aOR = 2.60, 95%CI:1.89-3.58), cervical injury with vertebral fracture (aOR = 2.19, 95%CI: 1.90-2.52), and severe liver disease (aOR = 2.33, 95%CI: 1.34-4.04) were all strong independent predictors of in-hospital mortality. In addition, malnutrition (aOR = 3.19, 95% CI: 2.93-3.48) was the strongest predictors of prolonged length of stay (LOS). CONCLUSIONS: Several critical factors for in-hospital mortality, unfavorable discharge, and prolonged LOS among US older adults with acute non-traffic tSCI were identified. In addition to the factors associated with initial severity, the presence of severe liver disease and malnutrition emerged as strong predictors of unfavorable outcomes, highlighting the need for special attention for these patient subgroups.

Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study.

OBJECTIVE: Functional MRI (fMRI) can be employed to assess neuronal activity in the central nervous system. However, investigating the spinal cord using fMRI poses several technical difficulties. Enhancing the fMRI signal intensity in the spinal cord can improve the visualization and analysis of different neural pathways, particularly those involved in bladder function. The bulbocavernosus reflex (BCR) is an excellent method for evaluating the integrity of the sacral spinal cord. Instead of stimulating the glans penis or clitoris, the BCR can be simulated comfortably by tapping the suprapubic region. In this study, we explain the necessity and development of a device to elicit the simulated BCR (sBCR) via suprapubic tapping while conducting an fMRI scan. METHODS: The device was successfully tested on a group of 20 healthy individuals. Two stimulation task block protocols were administered (empty vs. full bladder). Each block consisted of 40 s of suprapubic tapping followed by 40 s of rest, and the entire sequence was repeated four times. RESULTS: Our device can reliably and consistently elicit sBCR noninvasively as demonstrated by electromyographic recording of pelvic muscles and anal winking. Participants did note mild to moderate discomfort and urge to void during the full bladder task. CONCLUSION: Our device demonstrates an efficacious approach to elicit sBCR within an MRI bore to assess sacral spinal cord functional activity without generating any significant motion artifacts. SIGNIFICANCE: This device can explore the mechanisms and processes controlling urinary, digestive, or sexual function within this region in humans.

Development of an activity-based therapy tracking tool: Item generation and reduction using the Delphi method.

CONTEXT/OBJECTIVE: Activity-based therapies (ABT) are increasingly used in rehabilitation after spinal cord injury or disease (SCI/D). However, the absence of standardized tools to track the details of an ABT program hinders the collection of data needed for client-tailored programming and resource allocation. The objective of this study is to determine the content to include in an ABT tracking tool for people living with SCI/D. DESIGN: Cross-sectional e-survey. SETTING: Community. PARTICIPANTS: The 60 participants from Canada and the United States who had knowledge and/or experience with ABT included: individuals with SCI/D; hospital clinicians (i.e. physical and occupational therapists/assistants); community-based clinicians; hospital or community clinic administrators; researchers; and funders, advocates and policy makers. INTERVENTIONS: None. OUTCOME MEASURES: A Delphi e-survey comprised 16 types of ABT (e.g. treadmill training) and 4 types of technology (e.g. virtual reality). Participants rated the importance of including each item on a tracking tool and the feasibility to track each item using a 9-point Likert scale. RESULTS: After two survey rounds, nine types of ABT and one technology were identified as important to include in a tracking tool. All items rated as important were considered feasible for clinicians and people with SCI/D to track, except crawling. CONCLUSION: This study identified the types of ABT and technology to include in an ABT tracking tool. Such a tool may provide details of an ABT program that can support decision-making at the individual, program and health system levels and aid the development of best practice guidelines.

Determinants of prolonged baseline blood pressure restoration following autonomic dysreflexia for individuals with spinal cord injuries.

OBJECTIVE: This study aimed to identify the determinants affecting the time required for blood pressure (BP) restoration after autonomic dysreflexia (AD) and to propose a new method for BP measurement in individuals with cervical spinal cord injury (SCI) who experience AD. METHODS: In a prospective, single-center observational study, participants' bladders were filled with body-temperature saline until reaching cystometric capacity, as confirmed by previous urodynamic studies. Restoration time (RT), defined as the time from the onset of voiding until BP returned to baseline, was measured during the morning voiding session. This session involved the use of a 10F hydrophilic transurethral catheter. Data were then compared with various clinical determinants including demographic, urodynamic, and cystographic variables. RESULTS: The study included 29 individuals with cervical SCI. Notable variations in RT were observed among individuals with differing levels of detrusor overactivity (DO) and bladder compliance. An inverse correlation was noted between RT and bladder compliance, whereas positive correlations were identified with maximal detrusor pressure, peak systolic BP (SBP), and the magnitude of BP changes. Factors associated with prolonged RT included injury completeness, bladder trabeculation, vesicoureteral reflux (VUR), DO, and changes in SBP. CONCLUSIONS: A significant association was found between BP elevation and prolonged RT. Determinants such as the severity of the SCI, bladder trabeculation, VUR, and DO were correlated with prolonged RT, considering their importance in the assessment of baseline BP following AD.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

10 kHz stimulation as rescue therapy for spinal cord stimulation trial failure or loss of efficacy: A retrospective study.

INTRODUCTION: Spinal cord stimulation (SCS) is currently used for the management of pain of different origin, and since its inception, many waveforms have been developed. Some patients experience no pain relief already during SCS trial, while other patients go through a loss of efficacy due to habituation after a variable period of satisfying pain control. Our retrospective study represents the first report exploring the potential role of 10 kHz stimulation as rescue therapy for patients who did not benefit not only from conventional stimulation but even from other waveforms during SCS trial or follow-up. METHODS: This study was conducted in Germany; we retrospectively enrolled patients with no pain relief during SCS trial or with loss of efficacy of other waveforms over time; and we recorded visual analogic scale (VAS), Oswestry Disability Index (ODI), and daily opioid consumption expressed as morphine milligram equivalents (MME), right before and 12 months after the switching to 10 kHz simulation. RESULTS: The rate of successful switching to 10 kHz stimulation was comparable in patients enrolled during the SCS trial and during the follow-up (43% vs. 40%, respectively); notably, the highest rate of failed rescue was recorded in case of persistent spinal pain syndrome (PSPS) II. Patients who responded to the switching showed a significant improvement in VAS and ODI after 12 months of treatment compared to baseline (3.6 ± 1.0 vs. 8.2 ± 0.9, p < 0.00001 and 34.0 ± 7.8 vs. 64.3 ± 8.7, p < 0.0001, respectively), whereas there was no reduction in the consumption of opioids in terms of MME (3 (0-16) vs. 5 (0-8.75), p = 0.1003). CONCLUSIONS: Rescue therapy with 10 kHz stimulation could be an important strategy to avoid SCS explant in both patients non-responsive during trial or experiencing a loss of efficacy during the years with other waveforms.

Spinal cord stimulator paddle lead revision and replacement for misplaced or displaced electrodes.

OBJECTIVES: Spinal cord stimulators (SCS) are commonly implanted via a laminotomy or laminectomy. Revision surgery may be necessary in instances of hardware failure or loss of efficacy. It is uncommon for leads to have been initially misplaced in a suboptimal position, and revision in these cases necessitates additional dissection for appropriate repositioning. Accordingly, there is concern with a more extensive revision for a potentially higher risk of associated complications. This study aims to describe a series of patients with failed paddle SCS electrodes due to misplacement who underwent revision and replacement. METHODS: Patients who underwent SCS paddle replacement for misplaced paddles between 2021 and 2023 were identified. Medical charts were reviewed for demographic data, operative details, and incidence of complications. RESULTS: Sixteen patients underwent thoracic SCS paddle revision and replacement. The mean age was 59.6±12.6 years, with 11 females and 5 males. Misplaced paddles were too lateral (n=12), too high (n=2), or incompletely within the epidural space (n=2). The mean duration from initial implantation to revision surgery was 44.8±47.5 months. The mean operative duration was 126.1±26.9 minutes, and all patients required a "skip" laminectomy or laminotomy. No complications were encountered. The mean length of follow-up was 18.4±7.3 months. Mean preoperative pain intensity was 7.9±1.5, and at last follow-up was 3.6±1.7 (p<0.001). All but one patient continued to use their device in follow-up. CONCLUSION: The revision and replacement of misplaced paddle SCS electrodes is a feasible and durable revision strategy, even in long-term implants with extensive scarring.

OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/ß-Catenin Signaling Pathways.

Spinal cord injury (SCI) is a significant health concern, as it presently has no effective treatment in the clinical setting. Inflammation is a key player in the pathophysiological process of SCI, with a number of studies evidencing that the inhibition of the NF-κB signaling pathway may impede the inflammatory response and improve SCI. OTULIN, as a de-ubiquitination enzyme, the most notable is its anti-inflammatory effect. OTULIN can inhibit the NF-κB signaling pathway to suppress the inflammatory reaction via de-ubiquitination. In addition, OTULIN may promote vascular regeneration through the Wnt/ß-catenin pathway in the wake of SCI. In this review, we analyze the structure and physiological function of OTULIN, along with both NF-κB and Wnt/ß-catenin signaling pathways. Furthermore, we examine the significant role of OTULIN in SCI through its impairment of the NF-κB signaling pathway, which could open the possibility of it being a novel interventional target for the condition.

Canine glioma in the first year of life: 5 cases.

Most canine gliomas occur in adult and aged dogs, and reports in puppies < 12-mo-old are exceedingly rare. Here we describe the occurrence of gliomas in 5 dogs ≤ 12-mo-old. The affected patients (4 males, 1 female) were 3-12-mo-old (x̄ = 6.6-mo-old). None of the dogs were brachycephalic. Clinical signs consisted of dullness (2 cases), seizures (2 cases), vestibular signs, and deafness (1 case each). All patients were euthanized. Grossly, neoplasms were pale-tan or red, soft masses in the telencephalon (4 cases) or gelatinous leptomeningeal thickening in the brain and spinal cord (1 case). Neoplasms were classified as astrocytomas (3 cases) and oligodendrogliomas (2 cases) based on histology or histology and IHC. Our findings confirm that, while exceptionally rare, canine gliomas occur in the first year of life, and are clinically, morphologically, and immunohistochemically similar to gliomas in adult and aged dogs.

Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study.

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

Defining malnutrition in persons with spinal cord injury - does the Global Criteria for Malnutrition work?

Background and aims: Physiologic and metabolic changes following spinal cord injury (SCI) lead to an increased risk of malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) is a three-step approach to diagnose malnutrition: 1) screening; 2) phenotypic and etiological criteria; and 3) malnutrition severity. The main aim of this study was to assess malnutrition in patients with SCI, according to the GLIM criteria. Methods: Patients with SCI (≥ 18 years) admitted to rehabilitation were included. Anthropometrics, food intake, and inflammation were assessed on admission. Fat-free mass index (FFMI) was estimated from bioimpedance analysis. Malnutrition was diagnosed by the GLIM criteria, using the Malnutrition Universal Screening Tool (MUST) as the first step screening tool. Sensitivity and specificity analyses were performed. Results: In total, 66 patients were assessed (50 men) with a mean age of 51.4 (± 17.4) years and median time since injury was 37.5 (10-450) days. The mean body mass index was 24.7 (± 4.2) kg/m2, and 1-month involuntary weight loss was 5.7 (± 4.4)%. FFMI for men was 17.3 (± 1.9) and for women 15.3 (± 1.6) kg/m2. Forty-one patients (62%) were malnourished according to the GLIM criteria: 27 moderately and 14 severely malnourished. MUST was not able to detect malnutrition risk of nine patients, giving a moderate agreement (kappa 0.66), with a sensitivity of 0.78 and a specificity of 0.92 compared to the GLIM diagnosis. Conclusions: In this cross-sectional study, 62% of subacute SCI patients were malnourished according to the GLIM criteria. The screening tool MUST showed moderate agreement with the GLIM criteria and did not detect risk of all patients with a malnutrition diagnosis. The clinical implications of these findings need further investigation.

Cognitive, behavioral and psychiatric symptoms in patients with spinal cord injury: a scoping review.

Spinal Cord Injury (SCI) is a condition where the spinal cord is damaged and experiences partial or complete loss of motor and/or sensory function, which is typically less than normal. After SCI, patients may exhibit more severe psychiatric symptoms and experience cognitive impairments, including reduced speed and attention processing capacity, as well as difficulties with executive function and episodic memory retention. Among the behavioral and psychiatric symptoms, depression, anxiety, substance use disorder, and posttraumatic stress disorder are the most common. This review aims to investigate the cognitive, behavioral, or psychiatric symptoms of the patient with SCI and their influence on the rehabilitation process. Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases. Studies published between 2013-2023 were selected. This review has been registered on OSF (n) 3KB2U. We have found that patients with SCI are at high risk of cognitive impairment and experience a wide range of difficulties, including tasks based on processing speed and executive function. This clinical population may experience adjustment disorders with depression and anxiety, as well as other psychiatric symptoms such as fatigue, stress, and suicidal ideation. This review has demonstrated that SCI patients may experience psychiatric symptoms and cognitive impairments that affect their functioning. At the same time, these patients may be more prone to various adjustment and mood disorders. Moreover, these two aspects may interact with each other, causing a range of symptoms, increasing the risk of hospitalization, and delaying the rehabilitation process.

Inhibition of phospholipase D promotes neurological function recovery and reduces neuroinflammation after spinal cord injury in mice.

Introduction: Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation is one of the main pathophysiological features of secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), a critical lipid-signaling molecule, is known to be involved in various physiological processes, including the regulation of inflammation. Despite this knowledge, the specific role of PLD in SCI remains unclear. Methods: In this study, we constructed mouse models of SCI and administered PLD inhibitor (FIPI) treatment to investigate the efficacy of PLD. Additionally, transcriptome sequencing and protein microarray analysis of spinal cord tissues were conducted to further elucidate its mechanism of action. Results: The results showed that PLD expression increased after SCI, and inhibition of PLD significantly improved the locomotor ability, reduced glial scarring, and decreased the damage of spinal cord tissues in mice with SCI. Transcriptome sequencing analysis showed that inhibition of PLD altered gene expression in inflammation regulation. Subsequently, the protein microarray analysis of spinal cord tissues revealed variations in numerous inflammatory factors. Biosignature analysis pointed to an association with immunity, thus confirming the results obtained from transcriptome sequencing. Discussion: Collectively, these observations furnish compelling evidence supporting the anti-inflammatory effect of FIPI in the context of SCI, while also offering important insights into the PLD function which may be a potential therapeutic target for SCI.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Quantity, distribution and phenotype of newly generated cells in the intact spinal cord of adult macaque monkeys.

The existence of proliferating cells in the intact spinal cord, their distribution and phenotype, are well studied in rodents. A limited number of studies also address the proliferation after spinal cord injury, in non-human primates. However, a detailed description of the quantity, distribution and phenotype of proliferating cells at different anatomical levels of the intact adult non-human primate spinal cord is lacking at present. In the present study, we analyzed normal spinal cord tissues from adult macaque monkeys (Macaca fuscata), infused with Bromo-2'-deoxyuridine (BrdU), and euthanized at 2h, 2 weeks, 5 weeks and 10 weeks after BrdU. We found a significantly higher density of BrdU + cells in the gray matter of cervical segments as compared to thoracic or lumbar segments, and a significantly higher density of proliferating cells in the posterior as compared to the anterior horn of the gray matter. BrdU + cells exhibited phenotype of microglia or endothelial cells (∼50%) or astroglial and oligodendroglial cells (∼40%), including glial progenitor phenotypes marked by the transcription factors Sox9 and Sox10. BrdU + cells also co-expressed other transcription factors known for their involvement in embryonic development, including Emx2, Sox1, Sox2, Ngn1, Olig1, Olig2, Olig3. In the central canal, BrdU + cells were located along the dorso-ventral axis and co-labeled for the markers Vimentin and Nestin. These results reveal the extent of cellular plasticity in the spinal cord of non-human primates under normal conditions.

Acupuncture for radicular pain: a review of analgesic mechanism.

Radicular pain, a common and complex form of neuropathic pain, presents significant challenges in treatment. Acupuncture, a therapy originating from ancient traditional Chinese medicine and widely utilized for various pain types, including radicular pain, has shown promising outcomes in the management of lumbar radicular pain, cervical radicular pain, and radicular pain due to spinal stenosis. Despite its efficacy, the exact mechanisms through which acupuncture achieves analgesia are not fully elucidated and are the subject of ongoing research. This review sheds light on the current understanding of the analgesic mechanisms of acupuncture for radicular pain, offering valuable perspectives for both clinical application and basic scientific research. Acupuncture is postulated to relieve radicular pain by several mechanisms: peripherally, it reduces muscle spasms, lessens mechanical pressure on nerve roots, and improves microcirculation; at the molecular level, it inhibits the HMGB1/RAGE and TLR4/NF-κB signaling pathways, thereby decreasing the release of pro-inflammatory cytokines; within the spinal cord, it influences synaptic plasticity; and centrally, it modulates brain function, particularly affecting the medial prefrontal cortex, anterior cingulate cortex, and thalamus within the default mode network. By acting across these diverse biological domains, acupuncture presents an effective treatment modality for radicular pain, and deepening our understanding of the underlying mechanisms regarding analgesia for radicular pain is crucial for enhancing its clinical efficacy and advancement in pain management.

A multicenter study of the mid-term outcomes of patients with uncomplicated type B aortic dissection after distal porous Talos stent-graft implantation.

OBJECTIVES: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia. This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety endpoint was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy endpoint was treatment success at 12 months post-operation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at four levels, and spinal cord ischemia was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.