Spinal Cord Level Research Articles

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

New insights in the mechanisms of opioid analgesia and tolerance: ultramicronized palmitoylethanolamide down-modulates vascular endothelial growth factor-A in the nervous system

Growing evidence suggest that opioid analgesics modulate angiogenesis during pathophysiological processes. Vascular endothelial growth factor-A (VEGF-A) was recently proposed to be involved in pain development. To date, no anti-angiogenic drug is used for pain management. When administered in a bioavailable formulation, (i.e., ultramicronized) N-palmitoylethanolamine (PEA) delays the onset of morphine tolerance, improves morphine analgesic activity and reduces angiogenesis in in vivo models. This study aimed at investigating whether VEGF-A is involved in PEA-induced delay of morphine tolerance. The anti-VEGF-A monoclonal antibody bevacizumab was used as a reference drug. Preemptive and concomitant treatment with ultramicronized PEA delayed morphine tolerance and potentiated the analgesic effect of morphine, while counteracting morphine-induced increase of VEGF-A in the nervous system. Similar results were obtained when bevacizumab was administered together with morphine. Of note, bevacizumab showed an analgesic effect per se. In equianalgesic treatment regimens (obtained through increasing morphine doses and associating PEA), PEA resulted in lower expression of VEGF-A in dorsal root ganglia (DRG) and spinal cord compared to morphine alone. Similar results were observed for plasma levels of the soluble VEGF receptor 1 (sFLT-1). Moreover, in morphine treated animals, two pain related genes (i.e., Serpina3n and Eaat2) showed a more than 3-fold increase in their expression at spinal cord and DRG level, with the increase being significantly counteracted by PEA treatment. This study supports the hypothesis that the effects of PEA on morphine analgesia and tolerance may be mediated by the down-modulation of VEGF-A and sFLT-1 in the nervous system and plasma, respectively.

Clinical Risk Factors Associated with the Need for Tracheostomy in Traumatic Cervical and High Thoracic Spinal Cord Injury

BackgroundOur objective was to assess the association of completeness and level of spinal cord injury (SCI) with the need for tracheostomy and identify additional risk factors predictive of tracheostomy. MethodsThis was a retrospective review of patients with SCI between January 2017 and December 2022. ResultsPatients with complete SCI were roughly thirty-three times more likely to have a tracheostomy when compared to incomplete injury (82% vs 12%, p<0.001, OR = 32.9). The rate of tracheostomy did not differ between spinal cord levels for complete (p=0.68) or incomplete (p=0.08) injuries. Penetrating injury, low GCS, high ISS, and polytrauma were associated with tracheostomy need in incomplete SCI. ConclusionComplete injury was statistically significantly associated with the need for tracheostomy while level of injury failed to reach significance. Patients with incomplete SCI that have certain clinical risk factors should be considered for early tracheostomy.

Long‐lasting behavioral and neurochemical effects of early‐life environmental enrichment in rats submitted to neonatal morphine administration

AbstractThe present study examined the medium‐ and long‐term effects of early environmental enrichment (EE) on neuromotor, nociceptive, cognitive, behavioral, and neurochemical parameters in newborn rats repeatedly exposed to morphine. The study employed 90 Wistar rats: 10 adult nulliparous females and 80 male pups. Litter was split into standard and EE housing. Following, half of each litter received saline (S) or morphine (M) injections, resulting in four groups: SC + S, EE + S, SC + M, and EE + M. EE was applied from PND1 to PND21, while morphine or saline was given daily (5 μg/s.c.) from PND8 to PND14. Neuromotor development was similar between groups. In the OF test, morphine reduced outer and total crossings, whereas EE increased inner crossings and rearings. Adult rats showed a decrease in outer and total crossings and grooming and an increase in rearing. EE increased the number of protected and unprotected head dipping. Adult rats showed an increase in protected head dipping. Adult rats showed a lower recognition index, and, when exposed to EE, a lower anxiety index and analgesia. EE increased brainstem and hippocampal BDNF levels. Adult rats had increased hypothalamus, spinal cord, and brainstem BDNF levels, an increase in the spinal cord, and decreased hypothalamus TNF‐α levels. This study demonstrated that early‐life EE raises BDNF levels in the brainstem and hippocampus of rats and modifies their behaviors (such as nociception, exploration, and anxiety) in a state‐dependent manner (morphine and age).

Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level.

Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.

Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis

ObjectivesThis study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS). MethodsEight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 μm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm. ResultsThe long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 μm, n = 24) and the lateral nucleus (49.41 ± 13.86 μm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 μm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 μm, n = 756, p < 0.001, Mann–Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 μm, p = 0.352) was not significantly different from that of controls. ConclusionMotor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons.

Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation.

A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by invivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.

Atlas-guided brain projection tracts: From regions of interest to tractography 3D rendering.

The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty-nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)-posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio-caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro-posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC-PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level.

Neuro-microcirculatory interrelationships in patients with kyphoscoliosis associated with neurological deficits

Background: The use of laser Doppler flowmetry with spectral wavelet analysis of blood flow fluctuations allows us to assess the functional state of thin unmyelinated nerve fibers and objectify the dynamics of recovery processes in patients with kyphoscoliotic spinal deformities associated with spinal cord compression. AIM: To study the features of neuromicrocirculatory relationships in patients with kyphoscoliosis associated with neurological deficits before and after surgical treatment. MATERIALS AND METHODS: 20 patients with spinal deformities associated with neurological deficits of varying severity were examined using the LDF method and operated on. Patients were examined before surgery, 1–2 weeks after surgery following regression of acute postoperative pain syndrome, 3–6 months, 6–12 months, and more than a year after surgery. The scope of the study included a general examination with a detailed assessment of the neurological status, radiation diagnostics (postural radiographs of the spine, computed tomography and magnetic resonance imaging of the spine with assessment of spinal canal stenosis). Patients with severe kyphoscoliotic deformities underwent CT myelography followed by the design of individual full-size 3D plastic models of the spine and myeloradicular structures. LDF with wavelet analysis was carried out at all periods of the survey. A perfusion study with determination of the average microcirculation was carried out at the level of the pad of the distal phalanx of the big toe using a two-channel LAKK-02 device with a semiconductor laser (sensing in the red Raman and infrared IR channels). The obtained LDF results were processed by spectral amplitude-frequency wavelet analysis to characterize microcirculation regulation factors in the ranges of sympathetic adrenergic regulation (0.02–0.046 Hz), sensory peptidergic influences (0.047–0.069 Hz), myogenic oscillations (0.07–0.145 Hz). RESULTS: After surgery, the activity of trophotropic sensory peptidergic nerve fibers, the values of perfusion of the microcirculatory channel increased and was maintained starting from the early postoperative period. Ergotropic sympathetic adrenergic activity was significantly decreased in the period of 6-12 months after surgery. Maximum mobilization of trophotropic neurogenic mechanisms of sanogenesis was observed in the period of 6-12 months after surgery. CONCLUSION: The obtained data indicate a significant participation of thin nerve fibers in the recovery processes after decompressive surgeries in the spinal canal zone and the creation of anatomical conditions for neurophysiological repair at the spinal cord level. The use of the LDF method with spectral wavelet analysis of blood flow fluctuations makes it possible to objectify the dynamics of thin unmyelinated nerve fibers and recovery processes in patients with kyphoscoliotic deformities of the spine associated with spinal cord compression.

Mechanisms and risk factors associated with spinal cord injury, facet fracture, and level of dislocation, in occupants with cervical spine dislocations sustained in motor vehicle crashes

Objective Motor vehicle crashes (MVCs) are the leading cause of cervical spine dislocation. The mechanisms underlying this injury are unclear, limiting the development of injury prevention devices and strategies. MVC databases contain occupant, medical, vehicle, and crash details that are not routinely collected elsewhere, providing a unique resource for investigating injury mechanisms and risk factors. In this study, a comprehensive standalone analysis of cervical spine dislocations captured in MVC databases was performed. Methods Epidemiologic, biomechanical, and injury data were extracted from three MVC databases. Logistic regression models were developed to determine the occupant, vehicle, and crash characteristics, as well as the global (inertial or impact) and regional (flexion, compression, etc.) loading mechanisms associated with the level of cervical spine dislocation (axial or sub-axial), and the occurrence of spinal cord injury (SCI) or facet fracture concomitant to dislocation. Results There was no association between global or regional injury mechanisms and the level of cervical spine dislocation. Sub-axial dislocations were typically due to head/face impact with the airbag or upper interior components, or a result of seatbelt restraint of the torso. Higher occupant age, lower BMI, partial/no ejection, and frontal and side configuration crashes (compared to rollovers) were associated with a higher likelihood of sub-axial, versus axial, dislocation. Amongst all dislocations, an increased likelihood of SCI was associated with impact injuries, airbag non-deployment, and complete ejection, while concomitant facet fracture was associated with the presence of regional compression. Severe crashes, partial ejections, and “utility vehicles” and “vans and trucks” (compared with “passenger vehicles”) were associated with a higher risk of facet fracture concomitant to sub-axial dislocation. Conclusion The findings of this study may be used to inform the loading modes to be simulated in future ex vivo or computational models seeking a better understanding of cervical spine dislocations.

Immediate vs. delayed venous thromboembolism prophylaxis following spine surgery: increased rate of unplanned reoperation for postoperative hematoma with immediate prophylaxis

BACKGROUND CONTEXTThere is significant variability in postoperative chemoprophylaxis protocols amongst spine providers due to perceived risks and benefits, but limited data on the topic. At our institution, both orthopaedic spine and neurosurgery departments utilize unfractionated subcutaneous heparin in identical dosages and frequency, with the only difference being time to initiation postoperatively. PURPOSETo evaluate the rate of symptomatic venous thromboembolism (VTEs) and unplanned reoperation for hematoma based on timing of chemoprophylaxis initiation. STUDY DESIGN/SETTINGSingle institution retrospective cohort study. PATIENT SAMPLEPatients undergoing elective spine surgery, excluding patients undergoing surgery in the setting of trauma, malignancy, or infection OUTCOME MEASURESOutcome measures included the diagnosis of a venous thromboembolism within 90 days of surgery and unplanned reoperation for a hematoma METHODSPatients undergoing elective spine surgery from 2017 to 2021 were grouped based on chemoprophylaxis protocol. In the “immediate” group, patients received subcutaneous heparin 5000 units every 8 hours starting immediately after surgery, and in the “delayed” group, patients received chemoprophylaxis starting postoperative day (POD)-2 for any decompressions and/or fusions involving a spinal cord level (i.e., L2 and above) and POD-1 for those involving only levels below the spinal cord (i.e., L3 to pelvis). A cox proportional hazards model was created to assess independent predictors of venous thromboembolic events, while a logistic regression was utilized for unplanned reoperations for hematoma. RESULTSOf 8,704 patients, a total of 98 (1.13%) VTE events occurred, of which 43 (0.49%) were pulmonary embolism. Fifty-four patients (0.62%) had unplanned reoperations for postoperative hematomas. On cox proportional hazards model analysis, immediate chemoprophylaxis was not protective of a venous thromboembolism (Hazard Ratio: 1.18, p=.436), but, it was a significant independent predictor for unplanned reoperation for hematoma on multivariable logistic regression modeling (Odds Ratio: 3.29, p<.001). CONCLUSIONSBoth chemoprophylaxis protocols in our study resulted in low rates of VTE and postoperative hematoma. However, our findings suggest that the delayed chemoprophylaxis protocol may mitigate postoperative hematoma formation without increasing the risk for a thrombotic event.

The Spatiotemporal Expression of SOCS3 in the Brainstem and Spinal Cord of Amyotrophic Lateral Sclerosis Mice.

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons from the brain and spinal cord. The excessive neuroinflammation is thought to be a common determinant of ALS. Suppressor of cytokine signaling-3 (SOCS3) is pathologically upregulated after injury/diseases to negatively regulate a broad range of cytokines/chemokines that mediate inflammation; however, the role that SOCS3 plays in ALS pathogenesis has not been explored. Here, we found that SOCS3 protein levels were significantly increased in the brainstem of the superoxide dismutase 1 (SOD1)-G93A ALS mice, which is negatively related to a progressive decline in motor function from the pre-symptomatic to the early symptomatic stage. Moreover, SOCS3 levels in both cervical and lumbar spinal cords of ALS mice were also significantly upregulated at the pre-symptomatic stage and became exacerbated at the early symptomatic stage. Concomitantly, astrocytes and microglia/macrophages were progressively increased and reactivated over time. In contrast, neurons were simultaneously lost in the brainstem and spinal cord examined over the course of disease progression. Collectively, SOCS3 was first found to be upregulated during ALS progression to directly relate to both increased astrogliosis and increased neuronal loss, indicating that SOCS3 could be explored to be as a potential therapeutic target of ALS.

MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.

Bone cancer pain (BCP), due to cancer bone metastasis and bone destruction, is a common symptom of tumors, including breast, prostate, and lung tumors. Patients often experience severe pain without effective treatment. Here, using a mouse model of bone cancer, we report that MOTS-c, a novel mitochondrial-derived peptide, confers remarkable protection against cancer pain and bone destruction. Briefly, we find that the plasma level of endogenous MOTS-c is significantly lower in the BCP group than in the sham group. Accordingly, intraperitoneal administration of MOTS-c robustly attenuates bone cancer-induced pain. These effects are blocked by compound C, an AMPK inhibitor. Furthermore, MOTS-c treatment significantly enhances AMPKα 1/2 phosphorylation. Interestingly, mechanical studies indicate that at the spinal cord level, MOTS-c relieves pain by restoring mitochondrial biogenesis, suppressing microglial activation, and decreasing the production of inflammatory factors, which directly contribute to neuronal modulation. However, in the periphery, MOTS-c protects against local bone destruction by modulating osteoclast and immune cell function in the tumor microenvironment, providing long-term relief from cancer pain. Additionally, we find that chronic administration of MOTS-c has little effect on liver, renal, lipid or cardiac function in mice. In conclusion, MOTS-c improves BCP through peripheral and central synergistic effects on nociceptors, immune cells, and osteoclasts, providing a pharmacological and biological rationale for the development of mitochondrial peptide-based therapeutic agents for cancer-induced pain.

Lumbar epidural electrical stimulation enhances respiration in mice

Spinal cord epidural electrical stimulation (EES) has emerged as a novel approach to modulate and interrogate the neural circuit(s) underlying sensorimotor functions in the past few decades. Recent studies have revealed that cervical EES can regulate respiration in both human subjects and animal models. Furthermore, coupled cervical and lumbar stimulations significantly increased the rhythmic motor outputs in both the cervical and lumbar spinal cord. We hypothesize that the lumbar and cervical coupling is underpinned by cervico-lumbar synaptic connections, and thus, EES at level of the lumbar spinal cord alone may also facilitate respiration via the cervico-lumbar circuit. In this study, we applied EES to the dorsal surface of the lumbar spinal cord between levels 1 and 6 (L1-6) in anesthetized mice. We found that rostral lumbar (L1-2) EES at a stimulation intensity of 0.5 mA elicited significantly higher respiratory frequency, tidal volume, and minute ventilation responses compared to the other lumbar levels (L3-4 and L5-6) tested at intensities ranging from 0.1-1.0 mA. The increased respiratory activity elicited by lumbar stimulation persisted even after the stimulation ceased. Using the optimal stimulation parameters that we identified, we further investigated the underlying mechanism of the lumbar EES-induced respiratory response by examining the neuronal activation patterns. Using immunostaining, we detected c-fos signals, a marker of neuronal activity, in the cervical spinal cord and brainstem after EES at L1-2 using 0.5 mA at 30Hz. This indicates that focal lumbar stimulation elicits remote neuronal activation in cervical spinal cord and brainstem, regions that contain respiration-related neural circuits. These findings suggest that lumbar EES may facilitate respiration by recruiting paraspinal respiratory circuits and potentially supra-spinal respiratory central pattern generator(s). This study provides insights into the development of novel approaches to restore normal respiratory patterns for patients with respiratory disorders, particularly spinal cord injuries. This work was supported by The Louis and Harold Price Foundation, H &amp; H Evergreen Foundation, Jonathan and Susan Dolgen Foundation, the National Institute of Drug Abuse (R01DA047637), and the National Institute of Neurological Disorders and Stroke (UH3NS119772) in the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Analysis of Ionomic Profiles of Spinal Cords in a Rat Model with Bone Cancer Pain.

Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear. The BCP rat model was constructed through inoculation of Walker 256 cells into the left tibia. Von Frey test, whole-cell patch-clamp recording and inductively coupled plasma mass spectrometry (ICP-MS) technologies were conducted for measuring tactile hypersensitivity, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of neurons of spinal slices, and ionome of spinal cord samples, respectively. Principal component analysis (PCA) was used to explore ionomic patterns of the spinal cord. The BCP rat model was successfully constructed through implantation of Walker 256 cells into the left tibia. The frequency and amplitude of mEPSCs of neurons in the spinal cord slices from the BCP model rats were notably greater than those in the sham control. In terms of ionomics, the spinal cord levels of two macroelements (Ca and S), four microelements (Fe, Mn, Li and Sr) and the toxic element Ti in the BCP group of rats were significantly increased by inoculation of Walker 256 cancer cells, compared to the sham control. In addition, the correlation patterns between the elements were greatly changed between the sham control and BCP groups. PCA showed that inoculation of Walker 256 cells into the tibia altered the overall ionomic profiles of the spinal cord. There was a significant separation trend between the two groups. Taken together, inoculation of Walker 256 cells into the left tibia contributes to BCP, which could be closely correlated by some elements. The findings provided novel information on the relationship between the ionome and BCP.

374 Feasibility of Postoperative Diffusion Weighted Imaging to Assess Neural Recovery in Cervical Spondylotic Myelopathy

INTRODUCTION: Following decompressive surgery for cervical spondylotic myelopathy (CSM), advanced diffusion-weighted MRI, such as diffusion basis spectrum imaging (DBSI), may hold significant value by quantifying and tracking spinal cord microstructure. However, there is a paucity of studies investigating this topic, likely due to challenges in resolving signal distortions from spinal instrumentation. METHODS: A single-center prospective study enrolled 50 CSM patients and 20 control patients. All patients underwent preoperative and repeat diffusion-weighted MRI at two-year follow-up. All CSM patients underwent decompressive cervical surgery. DBSI metrics were extracted from the C3 spinal cord level only to minimize image artifact and reduce partial volume effects. DBSI anisotropic tensors evaluated white matter tracts through fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. DBSI isotropic tensors assessed extra-axonal pathology through restricted and non-restricted fraction. RESULTS: Of 50 CSM patients, 27 patients underwent both baseline and postoperative diffusion-weighted MRI scans with sufficient quality for analysis. This included 15 mild, 7 moderate, and 5 severe CSM patients, who were followed up to 23.2 (5.6, range 11.1-32.8) months. All preoperative C3 DBSI measures were significantly different between CSM and control patients (p &lt; 0.001), except DBSI fractional anisotropy (p = 0.31). At two-year follow-up, the same significance pattern was found, except DBSI radial diffusivity lost statistical significance (p = 0.75). When assessing change in C3 DBSI measures, CSM patients exhibited significant decreases in DBSI radial diffusivity (p = 0.02). Among control patients, there was no significant difference in DBSI metrics between timepoints. CONCLUSIONS: DBSI may have potential in the postoperative setting to inform clinicians of white matter tract recovery after decompressive cervical surgery for CSM.

Pirfenidone's Potential for Motor Recovery following Spinal Cord Compression Injury

Objective: The aim of this research was to access the ability of pirfenidone in improving motor activity of hindlimbs in rats following compression injury to spinal cord. Study Design: Experimental lab-based study. Settings: Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Pakistan. Duration: From March 2020 to April 2023. Methods: Injury induction at the T7 spinal cord level was carried out using a 70gm force aneurysm clip in rats. The rats were divided into three groups: Group A received a daily placebo, Group B received a daily dose of pirfenidone at 200 mg/kg/day, and Group C received a daily dose of pirfenidone at 500 mg/kg/day. Each group was further subdivided into two sub-groups, labeled as Groups 1 and 2, each consisting of 5 rats. The experiment lasted for 14 and 28 days. On the final day, all rats underwent BBB scoring to evaluate the motor activity in their hind limbs. Results: BBB scores showed statistically significant differences both between and within groups. Among the SCI groups, those treated with pirfenidone displayed higher BBB scores compared to those without pirfenidone treatment. Conclusion: Pirfenidone may improve motor function post-spinal cord injury by reducing fibrosis, preventing collagen buildup in the core of glial scars, and reducing reactive astrocytosis in the scar's outer region. This dual action could promote axonal regeneration and enhance synaptic connections, aiding in neurological recovery.

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.

Mode of delivery alters sensitivity to thermal and chemical stimuli in adult rats: An experimental study.

The mode of delivery might prompt a long-lasting alteration in physiological and behavioral responsiveness in offspring. This study was intended to evaluate if the mode of delivery could alter sensitivity to thermal and chemical stimuli in female rats. 56 adult female Wistar rats (200-220 gr) that were born by vaginal or cesarean section (C-section) were used (n = 28/each). Inflammatory pain was induced by subcutaneous injection of formalin into the hind paw. The thermal nociceptive threshold was determined by tail-flick and hot plate tests. Besides, the Western blot test was used to evaluate the spinal cord levels of c-Fos and c-Jun proteins. Formalin-induced inflammation was significantly decreased in C-section group as compared to vaginally born rats (p 0.001). The baseline nociceptive threshed and morphine-induced analgesia were significantly increased in C-section groups in comparison to vaginally born rats. In addition, the levels of c-Fos and c-Jun proteins were significantly decreased in the spinal cord of C-section rats as compared to vaginally born animals (p 0.01). Morphine treatment could decrease the expression of c-Fos and c-Jun in the C-section group (p 0.05). Overall, C-section rats showed lower spinal nociceptive processing and neuronal activity later in life, compared to the vaginal born rats.

An analysis of the effect of motor experience on muscle synergy in the badminton jump smash

The jump smash is badminton's most aggressive technical manoeuvre, which is often the key to winning a match. This paper aims to explore the neuromuscular control strategies of advanced and beginner players when jumping smash in different ways. Collecting sEMG and kinematic data from 18 subjects with different motor experiences when jumping smash. Nonnegative Matrix Factorization and K-Means clustering were used to extract muscle synergies and exclude irrelevant combined synergies. Uncontrolled manifold analysis was then used to explore the association between synergies and shoulder stability. In addition, motor output at the spinal cord level was assessed by mapping sEMG to each spinal cord segment. The study found that advanced subjects could respond to different jump smash styles by adjusting the coordinated activation strategies of the upper-limb and postural muscles. Long-term training can induce a rapid decrease in the degree of co-variation of the synergies before contact with a shuttlecock to better cope with an upcoming collision. It is recommended that beginners should focus more on training the coordination of upper-limb muscles and postural muscles.