Basal Cell Carcinoma Formation Within A Spinal Cord Stimulator Surgical Scar: A Case Report.

Implanting neuromodulation devices requires that pain medicine physicians be well-versed in proper surgical technique and postoperative wound management. To be able to identify abnormal wound healing, a basic understanding of normal wound healing is required. When postoperative wounds deviate from expected healing, it is important that pain medicine physicians entertain a broad differential diagnosis, including nonsurgical dermatologic pathology.

Intrathecal Vector Delivery in Juvenile Rats via Lumbar Cistern Injection.

Gene therapy is a powerful technology to deliver new genes to a patient for the treatment of disease, be it to introduce a functional gene, inactivate a toxic gene, or provide a gene whose product can modulate the biology of the disease. The delivery method for the therapeutic vector can take many forms, ranging from intravenous infusion for systemic delivery to direct injection into the target tissue. For neurodegenerative disorders, it is often desirable to skew transduction towards the brain and/or spinal cord. The least invasive approach to target the entire central nervous system involves injection into the cerebrospinal fluid (CSF), allowing the therapeutic to reach a large fraction of the central nervous system. The safest approach to deliver a vector into the CSF is the lumbar intrathecal injection, where a needle is introduced into the lumbar cistern of the spinal cord. This technique, also known as a lumbar puncture, has been widely used in neonatal and adult rodents and in large animal models. While the technique is similar across species and developmental stages, subtle differences in size, structure, and elasticity of tissues surrounding the intrathecal space require accommodations in the approach. This article describes a method for performing lumbar puncture in juvenile rats to deliver an adeno-associated serotype 9 vector. Here, 25-35 µL of vector were injected into the lumbar cistern, and a green fluorescent protein (GFP) reporter was used to evaluate the transduction profile resulting from each injection. The benefits and challenges of this approach are discussed.

Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.

Objective.Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδand C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling.Approach.We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain.Main results.We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes.Significance.Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.

A Case Report of Fluoroscopically Guided Epidural Catheter Placement in a Parturient with History of Tethered Cord, Super-Morbid Obesity, and Risk for Difficult Airway.

Tethered cord syndrome results from adherence of the conus medullaris to the sacrum and may be associated with high complication rates from neuraxial anesthesia. We present the case of a 32-year-old gravida 2 para 0 patient with a history of lipomyelomeningocele (one of several types of spina bifida) and tethered cord status post repair, residual low-lying conus medullaris, supermorbid obesity (body mass index of 58), and Mallampati IV airway, who underwent successful fluoroscopically guided epidural catheter placement for vaginal delivery. Risks and benefits of epidural catheter utilization and methods of placement are reviewed.

Viability leads to the emergence of gait transitions in learning agile quadrupedal locomotion on challenging terrains.

Quadruped animals are capable of seamless transitions between different gaits. While energy efficiency appears to be one of the reasons for changing gaits, other determinant factors likely play a role too, including terrain properties. In this article, we propose that viability, i.e., the avoidance of falls, represents an important criterion for gait transitions. We investigate the emergence of gait transitions through the interaction between supraspinal drive (brain), the central pattern generator in the spinal cord, the body, and exteroceptive sensing by leveraging deep reinforcement learning and robotics tools. Consistent with quadruped animal data, we show that the walk-trot gait transition for quadruped robots on flat terrain improves both viability and energy efficiency. Furthermore, we investigate the effects of discrete terrain (i.e., crossing successive gaps) on imposing gait transitions, and find the emergence of trot-pronk transitions to avoid non-viable states. Viability is the only improved factor after gait transitions on both flat and discrete gap terrains, suggesting that viability could be a primary and universal objective of gait transitions, while other criteria are secondary objectives and/or a consequence of viability. Moreover, our experiments demonstrate state-of-the-art quadruped robot agility in challenging scenarios.

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells.

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.

SCIWORA. Una rara entidad clínica en la población pediátrica. Estudio ambispectivo / SCIWORA in children. A rare clinical entity: Ambispective study

Introducción: La lesión medular tipo SCIWORA es una entidad clínica con baja incidencia y alta repercusión funcional. El objetivo del estudio es la descripción epidemiológica de esta lesión y su evolución funcional con un seguimiento medio de 10 años. Material y métodos: Estudio analítico, longitudinal, de cohortes ambispectivo. Fueron evaluados 13 pacientes con el diagnóstico de SCIWORA en el periodo de estudio 2001-2022. Variables evaluadas: edad, sexo, días hasta la lesión medular, causa de lesión, imagen medular en la RM postraumatismo, nivel neurológico de lesión, ASIA ingreso/alta/5 años, SCIM III ingreso/alta/3 años, tipo de tratamiento empleado, empleo de terapia NASCIS III ingreso, tiempo de hospitalización, seguimiento medio. En octubre del 2022 fueron nuevamente evaluados en consultas externas mediante: cuestionario de discapacidad cervical (NDI)/Oswestry y cuestionario de calidad de vida validado en castellano para lesionados medulares (SV-QLI/SCI). Resultados: La mediana de edad fue de 4 años, 77% varones. El 54% de las lesiones corresponden a nivel cervical. El ASIA al ingreso fue del 31% A y del 31% C, nivel neurológico: C2 (22%) y T10 (15%), tráfico como causa de lesión (77%), SCIM III ingreso/alta: 28,5/42. La estancia media hospitalaria fue de 115 días. NDI: 11,6 y Oswestry: 15,3. Conclusión: El 77% de los SCIWORA se producen en menores de 8 años. Al año del alta hospitalaria un 31% de los pacientes fueron catalogados como ASIA D y a los 5 años el porcentaje se mantiene constante. No se encontraron diferencias significativas entre la causa de la lesión y tipo de alteración en RM (p = 0,872), ni entre la edad y el tipo de lesión medular objetivada en RM (p = 0,149).(AU)

Introduction: SCIWORA has a low incidence but a high functional repercussion. The aim of the present study was to characterize the epidemiology of this clinical-radiological condition and evaluate functional outcome with a mean of 10-years follow-up. Material and methods: Observational, longitudinal ambispective cohort study. Thirteen SCIWORA patients were admitted in the study period. Demographics, mechanism of injury, spinal cord MRI findings, neurological level of injury, time to SCI, neurological status (AIS) at admission/discharge/5 years, spinal cord independence measure (SCIM III) scale at admission and discharge, hospital length of stay and mean follow-up were recorded. On October 2022 patients were re-evaluated using NDI, Oswestry, and SV-QLI/SCI. Results: Median age was 4 years. The study population for this investigation was mostly men (77%). 54% of level of injury correspond to cervical spine. AIS at admission was A (31%) and C (31%). Neurological level of injury was C2 (22%) and T10 (15%). Motor vehicle-related injury was the most prevalent mechanism of injury (77%), SCIM III scale at admission and discharge: 28.5/42, hospital length of stay was 115 days. The NDI was 11.6, Oswestry: 15.3 and SV-QLI/SCI: 17. Conclusions: Seventy-seven percent of SCIWORA patients was detected under 8 years-old. At 1 year follow-up after discharge 31% patients were AIS grade D and with 5 years follow-up the percentage remain constant. No statistically significant differences in the mechanism of injury and MRI findings (P = 0.872), age and MRI spinal cord findings (P = 0.149) were found in SCIWORA patients.(AU)

Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn.

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.

Two inhibitory neuronal classes govern acquisition and recall of spinal sensorimotor adaptation.

Spinal circuits are central to movement adaptation, yet the mechanisms within the spinal cord responsible for acquiring and retaining behavior upon experience remain unclear. Using a simple conditioning paradigm, we found that dorsal inhibitory neurons are indispensable for adapting protective limb-withdrawal behavior by regulating the transmission of a specific set of somatosensory information to enhance the saliency of conditioning cues associated with limb position. By contrast, maintaining previously acquired motor adaptation required the ventral inhibitory Renshaw cells. Manipulating Renshaw cells does not affect the adaptation itself but flexibly alters the expression of adaptive behavior. These findings identify a circuit basis involving two distinct populations of spinal inhibitory neurons, which enables lasting sensorimotor adaptation independently from the brain.

[Therapeutic mechanism of basic fibroblast growth factor on spinal cord injury in rats based on the Notch/signal transducer and activator of transcription 3 signaling pathway].

Objective: To explore the therapeutic effect of basic fibroblast growth factor (bFGF) on spinal cord injury (SCI) in rats and the influence of Notch/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods: A total of 40 10-week-old male Sprague Dawley (SD) rats were selected to establish T 10-segment SCI model by a free falling object. Among them, 32 successful models were randomly divided into model group and bFGF group, with 16 in each group. Another 16 SD rats were selected as sham-operation group, with only T 10 processes, dura mater, and spinal cord exposed. After modeling, the rats in bFGF group were intraperitoneally injected with 100 µg/kg bFGF (once a day for 28 days), and the rats in model group and sham-operation group were injected with normal saline in the same way. The survival of rats in each group were observed after modeling. Basso-Beattie-Bresnahan (BBB) scores were performed before modeling and at immediate, 14 days, and 28 days after modeling to evaluate the functional recovery of hind limbs. Then, the spinal cord tissue at the site of injury was taken at 28 days and stained with HE, Nissl, and propidium iodide (PI) to observe the pathological changes, neuronal survival (number of Nissl bodies) and apoptosis (number of PI red stained cells) of the spinal cord tissue; immunohistochemical staining and ELISA were used to detect the levels of astrocyte activation markers [glial fibrillary acidic protein (GFAP)] and inflammatory factors [interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ)] in tissues, respectively. Western blot was used to detect the expressions of Notch/STAT3 signaling pathway related proteins [Notch, STAT3, phosphoryl-STAT3 (p-STAT3), bone morphogenetic protein 2 (BMP-2)] in tissues. Results: All rats survived until the experiment was completed. At immediate after modeling, the BBB scores in model group and bFGF group significantly decreased when compared to sham-operation group ( P<0.05). At 14 and 28 days after modeling, the BBB scores in model group significantly decreased when compared to sham-operation group ( P<0.05); the bFGF group showed an increase compared to model group ( P<0.05). Compared with before modeling, the BBB scores of model group and bFGF group decreased at immediate after modeling, and gradually increased at 14 and 28 days, the differences between different time points were significant ( P<0.05). The structure of spinal cord tissue in sham-operation group was normal; in model group, there were more necrotic lesions in the spinal cord tissue and fewer Nissl bodies with normal structures; the number of necrotic lesions in the spinal cord tissue of the bFGF group significantly reduced compared to the model group, and some normally structured Nissl bodies were visible. Compared with sham-operation group, the number of Nissl bodies in spinal cord tissue significantly decreased, the number of PI red stained cells, GFAP, IL-1ß, TNF-α, IFN-γ, Notch, p-STAT3 /STAT3, BMP-2 protein expression levels significantly increased in model group ( P<0.05). The above indexes in bFGF group significantly improved when compared with model group ( P<0.05). Conclusion: bFGF can improve motor function and pathological injury repair of spinal cord tissue in SCI rats, improve neuronal survival, and inhibit neuronal apoptosis, excessive activation of astrocytes in spinal cord tissue and inflammatory response, the mechanism of which may be related to the decreased activity of Notch/STAT3 signaling pathway.

Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Effect of flipped venous catheter combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury.

OBJECTIVE: This study aimed to explore the effect of flipped venous catheters combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury. PATIENTS AND METHODS: 160 patients with hip dislocation and sciatic nerve injury were divided into conventional release and flipped catheter + electrical stimulation groups according to the treatment methods (n=80). Motor nerve conduction velocity (MCV) and lower limb motor function were compared. Serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were compared. The frequency of complications and quality of life were also compared. RESULTS: The MCV levels of the common peroneal nerve and tibial nerve in the flipped catheter + electrical stimulation group were greater than the conventional lysis group (p<0.05). After treatment, the lower extremity motor score (LMEs) in the flipped catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). The serum levels of BDNF and NGF in the flip catheter + electrical stimulation group were higher than the conventional lysis group (p<0.05). The complication rate in the flipped catheter + electrical stimulation group was lower than in the conventional release group (6.25% vs. 16.25%, p<0.05). The quality-of-life score in the flip catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). CONCLUSIONS: The flipped venous catheter combined with spinal cord electrical stimulation can improve nerve conduction velocity, lower limb motor function, serum BDNF and NGF levels, reduce complications, and help improve the quality of life of sufferers with sciatic nerve injury. Chictr.org.cn ID: ChiCTR2400080984.

Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T.

INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies.

Microtubule polarity determines the lineage of embryonic neural precursor in zebrafish spinal cord.

The phenomenal diversity of neuronal types in the central nervous system is achieved in part by the asymmetric division of neural precursors. In zebrafish neural precursors, asymmetric dispatch of Sara endosomes (with its Notch signaling cargo) functions as fate determinant which mediates asymmetric division. Here, we found two distinct pools of neural precursors based on Sara endosome inheritance and spindle-microtubule enrichment. Symmetric or asymmetric levels of spindle-microtubules drive differently Sara endosomes inheritance and predict neural precursor lineage. We uncover that CAMSAP2a/CAMSAP3a and KIF16Ba govern microtubule asymmetry and endosome motility, unveiling the heterogeneity of neural precursors. Using a plethora of physical and cell biological assays, we determined the physical parameters and molecular mechanisms behind microtubule asymmetries and biased endosome motility. Evolutionarily, the values of those parameters explain why all sensory organ precursor cells are asymmetric in flies while, in zebrafish spinal cord, two populations of neural precursors (symmetric vs asymmetric) are possible.

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

CSF1R antagonism results in increased supraspinal infiltration in EAE.

BACKGROUND: Colony stimulating factor 1 receptor (CSF1R) signaling is crucial for the maintenance and function of various myeloid subsets. CSF1R antagonism was previously shown to mitigate clinical severity in experimental autoimmune encephalomyelitis (EAE). The associated mechanisms are still not well delineated. METHODS: To assess the effect of CSF1R signaling, we employed the CSF1R antagonist PLX5622 formulated in chow (PLX5622 diet, PD) and its control chow (control diet, CD). We examined the effect of PD in steady state and EAE by analyzing cells isolated from peripheral immune organs and from the CNS via flow cytometry. We determined CNS infiltration sites and assessed the extent of demyelination using immunohistochemistry of cerebella and spinal cords. Transcripts of genes associated with neuroinflammation were also analyzed in these tissues. RESULTS: In addition to microglial depletion, PD treatment reduced dendritic cells and macrophages in peripheral immune organs, both during steady state and during EAE. Furthermore, CSF1R antagonism modulated numbers and relative frequencies of T effector cells both in the periphery and in the CNS during the early stages of the disease. Classical neurological symptoms were milder in PD compared to CD mice. Interestingly, a subset of PD mice developed atypical EAE symptoms. Unlike previous studies, we observed that the CNS of PD mice was infiltrated by increased numbers of peripheral immune cells compared to that of CD mice. Immunohistochemical analysis showed that CNS infiltrates in PD mice were mainly localized in the cerebellum while in CD mice infiltrates were primarily localized in the spinal cords during the onset of neurological deficits. Accordingly, during the same timepoint, cerebella of PD but not of CD mice had extensive demyelinating lesions, while spinal cords of CD but not of PD mice were heavily demyelinated. CONCLUSIONS: Our findings suggest that CSF1R activity modulates the cellular composition of immune cells both in the periphery and within the CNS, and affects lesion localization during the early EAE stages.

Hypothermia effects on neuronal plasticity post spinal cord injury.

BACKGROUND: SCI is a time-sensitive debilitating neurological condition without treatment options. Although the central nervous system is not programmed for effective endogenous repairs or regeneration, neuroplasticity partially compensates for the dysfunction consequences of SCI. OBJECTIVE AND HYPOTHESIS: The purpose of our study is to investigate whether early induction of hypothermia impacts neuronal tissue compensatory mechanisms. Our hypothesis is that although neuroplasticity happens within the neuropathways, both above (forelimbs) and below (hindlimbs) the site of spinal cord injury (SCI), hypothermia further influences the upper limbs' SSEP signals, even when the SCI is mid-thoracic. STUDY DESIGN: A total of 30 male and female adult rats are randomly assigned to four groups (n = 7): sham group, control group undergoing only laminectomy, injury group with normothermia (37°C), and injury group with hypothermia (32°C +/-0.5°C). METHODS: The NYU-Impactor is used to induce mid-thoracic (T8) moderate (12.5 mm) midline contusive injury in rats. Somatosensory evoked potential (SSEP) is an objective and non-invasive procedure to assess the functionality of selective neuropathways. SSEP monitoring of baseline, and on days 4 and 7 post-SCI are performed. RESULTS: Statistical analysis shows that there are significant differences between the SSEP signal amplitudes recorded when stimulating either forelimb in the group of rats with normothermia compared to the rats treated with 2h of hypothermia on day 4 (left forelimb, p = 0.0417 and right forelimb, p = 0.0012) and on day 7 (left forelimb, p = 0.0332 and right forelimb, p = 0.0133) post-SCI. CONCLUSION: Our results show that the forelimbs SSEP signals from the two groups of injuries with and without hypothermia have statistically significant differences on days 4 and 7. This indicates the neuroprotective effect of early hypothermia and its influences on stimulating further the neuroplasticity within the upper limbs neural network post-SCI. Timely detection of neuroplasticity and identifying the endogenous and exogenous factors have clinical applications in planning a more effective rehabilitation and functional electrical stimulation (FES) interventions in SCI patients.

ß1 integrins play a critical role maintaining vascular integrity in the hypoxic spinal cord, particularly in white matter.

Interactions between extracellular matrix (ECM) proteins and ß1 integrins play an essential role maintaining vascular integrity in the brain, particularly under vascular remodeling conditions. As blood vessels in the spinal cord are reported to have distinct properties from those in the brain, here we examined the impact of ß1 integrin inhibition on spinal cord vascular integrity, both under normoxic conditions, when blood vessels are stable, and during exposure to chronic mild hypoxia (CMH), when extensive vascular remodeling occurs. We found that a function-blocking ß1 integrin antibody triggered a small degree of vascular disruption in the spinal cord under normoxic conditions, but under hypoxic conditions, it greatly enhanced (20-fold) vascular disruption, preferentially in spinal cord white matter (WM). This resulted in elevated microglial activation as well as marked loss of myelin integrity and reduced density of oligodendroglial cells. To understand why vascular breakdown is localized to WM, we compared expression levels of major BBB components of WM and grey matter (GM) blood vessels, but this revealed no obvious differences. Interestingly however, hypoxyprobe staining demonstrated that the most severe levels of spinal cord hypoxia induced by CMH occurred in the WM. Analysis of brain tissue revealed a similar preferential vulnerability of WM tracts to show vascular disruption under these conditions. Taken together, these findings demonstrate an essential role for ß1 integrins in maintaining vascular integrity in the spinal cord, and unexpectedly, reveal a novel and fundamental difference between WM and GM blood vessels in their dependence on ß1 integrin function during hypoxic exposure. Our data support the concept that the preferential WM vulnerability described may be less a result of intrinsic differences in vascular barrier properties between WM and GM, and more a consequence of differences in vascular density and architecture.

Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain.

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days. Results demonstrated that EA effectively attenuated CCI-induced pain hypersensitivity and mitigated neuron damage and loss in the spinal cord of NP rats. Moreover, EA reversed the oxidative stress-mediated spinal ferroptosis phenotype by upregulating reduced expression of xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) and superoxide dismutase (SOD) levels, and downregulating increased expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), malondialdehyde levels and iron overload. Furthermore, EA increased the immunofluorescence co-staining of GPX4 in neurons cells of the spinal cord of CCI rats. Mechanistic analysis unveiled that the inhibition of antioxidant pathway of Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal ferroptosis in NP rats while marginally diminishing its analgesic effect. These findings suggest that EA treatment at acupoints ST36 and GV20 may protect against NP by inhibiting neuronal ferroptosis in the spinal cord, partially through the activation of Nrf2 signalling.