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JCI Insight May 2024Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel...
Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.
Topics: Animals; Neuralgia; Ganglia, Spinal; Mice; Down-Regulation; Sensory Receptor Cells; Male; Peripheral Nerve Injuries; Mice, Inbred C57BL; Sciatic Nerve; Disease Models, Animal; Intermediate-Conductance Calcium-Activated Potassium Channels; Action Potentials
PubMed: 38912580
DOI: 10.1172/jci.insight.180085 -
Cureus Jun 2024Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment...
Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment neuropathy exist. In this prospective observational study, we investigated the differential compressions caused by wearing elastic stockings before and after anesthesia, as well as changes in the diameters of the lower leg and ankle in parturient women undergoing spinal anesthesia for elective cesarean section (CS). Methods Eighteen pregnant women, classified by the American Society of Anesthesiologists as having physical status 2, underwent lower leg measurements taken before a CS. Elastic stockings were applied, and compression pressure was measured at pre-anesthesia, post-surgery, and six hours post-return to a hospital room. Fluid, blood loss, urine output, and neuropathy presence were recorded. For all parameters, changes at the three time points were compared for the primary analysis. For secondary analysis, participants were categorized as having intraoperative blood loss greater than (group P) or less than 1,000 g (group N), and factors were compared with pre-anesthesia and six hours post-return to a room. Data were analyzed and presented using a one-way analysis of variance with Bonferroni correction for multiple comparisons or unpaired two-tailed t-tests for pairwise comparison. Results None of the women had postoperative entrapment neuropathy. Six patients had >1,000 g of blood loss. Compression significantly increased from pre-anesthesia (left 13.6 ± 2.4, 95% CI: 12.18 to 14.52; right 13.4 ± 2.4, 95% CI: 12.41 to 14.69) to post-surgery (left, 17.4 ± 2.6, 95% CI: 15.68 to 18.12; right, 16.9 ± 2.6, 95% CI: 16.20 to 18.70) (p < 0.01). Compression pressure at post-surgery differed significantly between group P (left, 15.3 ± 1.3; right, 14.7 ± 1.8; 95% CI: -4.98 to -0.32) and group N (left, 18.1 ± 2.9; right, 17.8 ± 2.4; 95% CI: -5.38 to -0.26) (p < 0.05). The results are expressed as mean ± standard deviation, with P-values <0.05 indicating statistical significance. Conclusions In this study, no neuropathy occurred; however, over-compression risk with elastic stockings, especially when exceeding recommended pressure levels, was highlighted. Balancing thromboembolism prevention and over-compression risks is crucial for patients undergoing CSs with spinal anesthesia.
PubMed: 38912079
DOI: 10.7759/cureus.62809 -
JBMR Plus Jul 2024Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI). To date, most research has focused on pharmaceutical... (Clinical Trial)
Clinical Trial
Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI). To date, most research has focused on pharmaceutical intervention using antiresorptives to prevent bone loss during the acute phase of SCI; however, limited research has investigated treatments for established osteoporosis during chronic SCI. Romosozumab, a monoclonal antibody with both antiresorptive and anabolic effects, has demonstrated significant increases in BMD for women with established PMO. Therefore, the purpose of this study was to examine the efficacy of monthly treatment with romosozumab to improve DXA-derived areal BMD at the hip, and CT-derived BMC and strength at the hip and knee in women with chronic SCI and an inability to ambulate. Twelve female participants with chronic SCI were recruited to receive 1 yr of monthly subcutaneous injections of romosozumab (210 mg). DXA and CT scans were taken at baseline, and months 3, 6, and 12 to quantify bone mineral, and finite element (FE) analysis was used to predict bone strength. Longitudinal mixed effects models were employed to determine the impact of treatment on bone properties. After 12 mo of treatment, areal BMD at the lumbar spine and total hip were significantly increased with median changes of 10.2% (IQR: 8.3-15.2%, <.001) and 4.2% (IQR: 3.4-7.7%, = .009), respectively. Improvements at the hip were primarily due to increases in trabecular, not cortical, bone and effects were sufficient to significantly increase FE-predicted strength by 20.3% (IQR: 9.5-37.0%, = .004). Treatment with romosozumab did not lead to any significant improvement in bone mineral at the distal femur or proximal tibia. These findings provide promising results for romosozumab treatment to improve bone mineral and reduce fracture risk at the hip, but not the knee, in women with chronic SCI.
PubMed: 38911320
DOI: 10.1093/jbmrpl/ziae077 -
Cureus May 2024Atlantoaxial dislocations (AAD) are a diverse set of C1-C2 rotatory subluxations that include the inferior and superior axial facet articulations. C1-C2 segments are...
Atlantoaxial dislocations (AAD) are a diverse set of C1-C2 rotatory subluxations that include the inferior and superior axial facet articulations. C1-C2 segments are both covered by cranial-cervical ligaments, indicating that AAD would damage both joints. Whenever the posterior elements are missing or impaired, lateral mass screw fixation has replaced alternative posterior cervical fixation procedures as the preferred treatment for securing the sub-axial cervical spine. An increase in muscle tone, hyperreflexia, pathological reflexes, digit/hand clumsiness, and gait deviations caused by spinal cord compression at the cervical level are the most common clinical features. A 23-year-old female patient came with the chief complaint of weakness, tingling sensation, and numbness in both upper and lower limbs along with imbalance while walking. She had a history of falls which was managed conservatively. As the symptoms progressed, an MRI, a CT scan, and an X-ray of the neck were done to rule out the level of injury which revealed AAD, and the patient was operated on for C1-C2 lateral mass fixation. Post-operatively, the patient was referred to the physiotherapy department for further management. The patient's quality of life and daily functioning were positively affected after undergoing early intervention as measured by the Functional Independence Measure, Neck Disability Index, Berg Balance Scale, and Dynamic Gait Index.
PubMed: 38910634
DOI: 10.7759/cureus.60913 -
Cureus May 2024This case series investigates the efficacy of the "sashimi technique," a novel surgical approach utilizing a curved chisel for the resection of heterotopic ossification...
This case series investigates the efficacy of the "sashimi technique," a novel surgical approach utilizing a curved chisel for the resection of heterotopic ossification (HO). The main focus is on reducing resection margins and preventing excessive bone removal while maintaining optimal functional outcomes and preventing recurrence. Two cases illustrate successful outcomes in patients with spinal cord injuries and severe HO of the hip, emphasizing the precision of using the curved chisel-based technique in improving patient mobility while still achieving a desired resection margin. The study highlights the effectiveness of using a curved chisel in protecting neurovascular structures and maintaining resection precision. Additionally, the integration of postoperative radiotherapy and pharmacological treatment is emphasized as a strategy to prevent recurrence. The goal of this procedure is to improve functional outcomes and patient quality of life.
PubMed: 38910625
DOI: 10.7759/cureus.60966 -
Cell Transplantation 2024Transplantation of mesenchymal stem cells (MSCs) is one of the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less in humans,... (Meta-Analysis)
Meta-Analysis
Transplantation of mesenchymal stem cells (MSCs) is one of the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less in humans, and the optimal transplantation strategy for MSCs is still controversial. In this article, we explore the optimal transplantation strategy of MSCs through a network meta-analysis of the effects of MSCs on SCI in animal models. PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases were searched by computer for randomized controlled studies on MSCs for SCI. Two investigators independently completed the literature screening and data extraction based on the inclusion and exclusion criteria. RevMan 5.4 software was used to assess the quality of the included literature. Stata 16.0 software was used for standard meta-analysis and network meta-analysis. Standardized mean difference (SMD) was used for continuous variables to combine the statistics and calculate 95% confidence interval (95% CI). < 0.05 was considered a statistically significant difference. Cochrane's test and the value were used to indicate the magnitude of heterogeneity. A random-effects model was used if > 50% and < 0.10 indicated significant heterogeneity between studies, and conversely, a fixed-effects model was used. Evidence network diagrams were drawn based on direct comparisons between various interventions. The surface under the cumulative ranking curve area (SUCRA) was used to predict the ranking of the treatment effects of each intervention. A total of 32 animal studies were included in this article for analysis. The results of the standard meta-analysis showed that MSCs improved motor ability after SCI. The network meta-analysis showed that the best treatment effect was achieved for adipose tissue-derived mesenchymal stromal cells (ADMSCs) in terms of cell source and intrathecal (IT) in terms of transplantation modality. For transplantation timing, the best treatment effect was achieved when transplantation was performed in the subacute phase. The available literature suggests that IT transplantation using ADMSCs in the subacute phase may be the best transplantation strategy to improve functional impairment after SCI. Future high-quality studies are still needed to further validate the results of this study to ensure the reliability of the results.
Topics: Animals; Humans; Rats; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Network Meta-Analysis; Spinal Cord Injuries
PubMed: 38910431
DOI: 10.1177/09636897241262992 -
The Spine Journal : Official Journal of... Jun 2024Traumatic subaxial cervical spine fractures are a significant public health concern due to their association with spinal cord injuries (SCI). Despite being mostly caused...
BACKGROUND
Traumatic subaxial cervical spine fractures are a significant public health concern due to their association with spinal cord injuries (SCI). Despite being mostly caused by low-energy trauma, these fractures significantly contribute to morbidity and mortality. Currently, research regarding early mortality based on the choice of treatment following these fractures is limited. Identifying predictors of early mortality may aid in postoperative patient monitoring and improve outcomes.
PURPOSE
This study aimed to identify predictors of 30-days, 90-days, and one-year mortality in adults treated for subaxial fractures.
STUDY DESIGN
A retrospective review of the nationwide Swedish Fracture Register (SFR).
PATIENT SAMPLE
All adult patients in the SFR who underwent treatment for a subaxial cervical fracture (n = 1,963).
OUTCOME MEASURES
Analyzed variables included age, sex, injury mechanism, neurological function, fracture characteristics, and treatment type. The primary endpoints were 30-days, 90-days, and one-year mortality.
METHODS
1,963 patients in the SFR, treated for subaxial cervical fractures between 2013 to 2021, were analyzed. Surgical procedures included anterior, posterior, or anteroposterior approaches. Non-surgical treatment included collar treatment or medical examinations without intervention. Stepwise regression and Cox regression analysis were used to determine predictors. Model performance was tested using the area under the receiver operating characteristic curve (AUC).
RESULTS
620 patients underwent surgery and 1,343 received non-surgical treatment. Surgical cases had primarily translation fractures, with 323 (52%) displaying no neurological deficits. Mortality rates at 30 days, 90 days, and one year were 22/620 (3.5%), 35/620 (5.6%), and 53/620 (8.5%), respectively. Age and SCI were predictors of mortality. Non-surgically treated patients mostly had compression fracture, with 1,214 (90%) experiencing no neurological deficits. Mortality rates at 30 days, 90 days, and one year were 41/1,343 (3.1%), 71/1,343 (5.3%), and 118/1,343 (8.7%). Age, male sex, SCI and fractures occurring at the C3 or C6 levels were predictors of mortality. An intact neurological function was a positive predictor of survival among non-surgically treated patients (AUC > 0.78).
CONCLUSIONS
Age and SCI emerged as significant predictors of early mortality in both surgically and non-surgically treated patients. An intact neurological function served as a protective factor against early mortality in non-surgically treated patients. Fractures at C3 or C6 vertebrae may impact mortality.
PubMed: 38909908
DOI: 10.1016/j.spinee.2024.06.015 -
Lipids in Health and Disease Jun 2024Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype,...
BACKGROUND
Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved.
METHODS
C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM.
RESULTS
Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β.
CONCLUSION
These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
Topics: Animals; MicroRNAs; Microglia; Mice; Autophagy; Lipid Droplets; Mice, Inbred C57BL; Demyelinating Diseases; Cathepsin B; Lysophosphatidylcholines; Disease Models, Animal; Male; Gene Expression Regulation; Cell Line
PubMed: 38909243
DOI: 10.1186/s12944-024-02185-y -
BMC Neurology Jun 2024After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability...
BACKGROUND
After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.
OBJECTIVE
To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.
METHODS
This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.
DISCUSSION
The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.
TRIAL REGISTRATION NUMBER
ChiCTR2300068831.
Topics: Humans; Spinal Cord Injuries; Recovery of Function; Hand; Transcranial Magnetic Stimulation; Motor Cortex; Prospective Studies; Evoked Potentials, Motor; Male; Adult; Female; Cohort Studies; Middle Aged; Spectroscopy, Near-Infrared
PubMed: 38909175
DOI: 10.1186/s12883-024-03705-0 -
International Immunopharmacology Jun 2024Blood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI....
BACKGROUND
Blood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels.
METHODS
Human blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed.
RESULTS
DECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered.
CONCLUSION
Therefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.
PubMed: 38908081
DOI: 10.1016/j.intimp.2024.112505