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1.
A A Pract ; 18(4): e01777, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587314

RESUMO

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.


Assuntos
Anestesia Epidural , Defeitos do Tubo Neural , Obesidade Mórbida , Feminino , Humanos , Adulto , Obesidade Mórbida/complicações , Medula Espinal , Cateteres
2.
PLoS One ; 19(4): e0301430, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578715

RESUMO

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.


Assuntos
Hipotermia , Traumatismos da Medula Espinal , Humanos , Ratos , Masculino , Feminino , Animais , Traumatismos da Medula Espinal/terapia , Potenciais Somatossensoriais Evocados/fisiologia , Sistema Nervoso Central , Plasticidade Neuronal/fisiologia , Medula Espinal
3.
Cell Transplant ; 33: 9636897241241998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590295

RESUMO

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.


Assuntos
Traumatismos da Medula Espinal , Transplante de Células-Tronco , Humanos , Neurônios , Medula Espinal
4.
Nat Commun ; 15(1): 3073, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594288

RESUMO

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.


Assuntos
Marcha , Robótica , Animais , Caminhada , Medula Espinal , Encéfalo , Locomoção
5.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 68(2): 151-158, Mar-Abr. 2024. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-231897

RESUMO

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)


Assuntos
Humanos , Masculino , Feminino , Criança , Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Traumatologia , Estudos Longitudinais , Estudos de Coortes , Pediatria
6.
Artigo em Russo | MEDLINE | ID: mdl-38465825

RESUMO

Postherpetic neuralgia is a chronic and debilitating condition that can occur following an episode of herpes zoster (shingles). It is characterized by severe, persistent pain in the area where the shingles rash occurred. While various treatment approaches exist, including medications and non-invasive therapies, some cases of postherpetic neuralgia may require neurosurgical intervention. Neurosurgical treatment options for postherpetic neuralgia aim to alleviate the pain by targeting the affected nerves or neural pathways. One common approach is spinal cord stimulation (SCS). In SCS, electrodes are implanted along the spinal cord, and electrical impulses are delivered to interfere with the transmission of pain signals. This technique can modulate pain perception and significantly reduce the intensity and frequency of postherpetic neuralgia symptoms. Neurosurgical treatment of postherpetic neuralgia is typically considered when conservative measures have failed to provide sufficient relief. However, it is crucial for patients to undergo a comprehensive evaluation and consultation with a neurosurgeon to determine the most appropriate treatment approach based on their specific condition and medical history. The risks, benefits, and potential outcomes of neurosurgical interventions should be carefully discussed between the patient and their healthcare provider to make an informed decision.


Assuntos
Herpes Zoster , Neuralgia Pós-Herpética , Estimulação da Medula Espinal , Humanos , Neuralgia Pós-Herpética/cirurgia , Medula Espinal , Eletrodos
7.
J Vis Exp ; (204)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38465945

RESUMO

Experimental autoimmune encephalomyelitis (EAE) is a common immune-based model of multiple sclerosis (MS). This disease can be induced in rodents by active immunization with protein components of the myelin sheath and Complete Freund's adjuvant (CFA) or by the transfer of myelin-specific T effector cells from rodents primed with myelin protein/CFA into naïve rodents. The severity of EAE is typically scored on a 5-point clinical scale that measures the degree of ascending paralysis, but this scale is not optimal for assessing the extent of recovery from EAE. For example, clinical scores remain high in some EAE models (e.g., myelin oligodendrocyte glycoprotein [MOG] peptide-induced model of EAE) despite the resolution of inflammation. Thus, it is important to complement clinical scoring with histological scoring of EAE, which also provides a means to study the underlying mechanisms of cellular injury in the central nervous system (CNS). Here, a simple protocol is presented to prepare and stain spinal cord and brain sections from mice and to score inflammation, demyelination, and axonal injury in the spinal cord. The method for scoring leukocyte infiltration in the spinal cord can also be applied to score brain inflammation in EAE. A protocol for measuring soluble neurofilament light (sNF-L) in the serum of mice using a Small Molecule Assay (SIMOA) assay is also described, which provides feedback on the extent of overall CNS injury in live mice.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Encefalomielite Autoimune Experimental/induzido quimicamente , Esclerose Múltipla/patologia , Medula Espinal/patologia , Inflamação/patologia , Axônios/patologia , Glicoproteína Mielina-Oligodendrócito , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/efeitos adversos
8.
Biol Res ; 57(1): 8, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475854

RESUMO

The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.


Assuntos
Bainha de Mielina , Neuroglia , Neuroglia/fisiologia , Bainha de Mielina/fisiologia , Células-Tronco , Medula Espinal , Encéfalo
9.
Sci Transl Med ; 16(738): eadg3665, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478631

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents. Using electrocorticography in the Sod1G86R and FusΔNLS/+ ALS mouse models and standard electroencephalography recordings in patients with sporadic ALS, we demonstrate a deficit in theta-gamma phase-amplitude coupling (PAC) in ALS. In mice, PAC deficits started before symptom onset, and in patients, PAC deficits correlated with the rate of disease progression. Using mass spectrometry analyses of CNS neuropeptides, we identified a presymptomatic reduction of noradrenaline (NA) in the motor cortex of ALS mouse models, further validated by in vivo two-photon imaging in behaving SOD1G93A and FusΔNLS/+ mice, that revealed pronounced reduction of locomotion-associated NA release. NA deficits were also detected in postmortem tissues from patients with ALS, along with transcriptomic alterations of noradrenergic signaling pathways. Pharmacological ablation of noradrenergic neurons with DSP-4 reduced theta-gamma PAC in wild-type mice and administration of a synthetic precursor of NA augmented theta-gamma PAC in ALS mice. Our findings suggest theta-gamma PAC as means to assess and monitor cortical dysfunction in ALS and warrant further investigation of the NA system as a potential therapeutic target.


Assuntos
Esclerose Amiotrófica Lateral , Doenças do Sistema Nervoso Autônomo , Dopamina beta-Hidroxilase/deficiência , Doenças Neurodegenerativas , Norepinefrina/deficiência , Humanos , Camundongos , Animais , Esclerose Amiotrófica Lateral/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Doenças Neurodegenerativas/metabolismo , Medula Espinal/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Superóxido Dismutase/metabolismo
10.
Nat Commun ; 15(1): 2189, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467605

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.


Assuntos
Esclerose Amiotrófica Lateral , Doenças Neurodegenerativas , Humanos , Camundongos , Animais , Idoso , Esclerose Amiotrófica Lateral/metabolismo , Doenças Neurodegenerativas/metabolismo , Camundongos Transgênicos , Neurônios Motores/metabolismo , Medula Espinal/metabolismo
11.
Sci Rep ; 14(1): 5929, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467696

RESUMO

The copper compound CuII(atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) is neuroprotective in mutant SOD1 mouse models of ALS where its activity is ascribed in part to improving availability of essential copper. However, SOD1 mutations cause only ~ 2% of ALS cases and therapeutic relevance of copper availability in sporadic ALS is unresolved. Herein we assessed spinal cord tissue from human cases of sporadic ALS for copper-related changes. We found that when compared to control cases the natural distribution of spinal cord copper was disrupted in sporadic ALS. A standout feature was decreased copper levels in the ventral grey matter, the primary anatomical site of neuronal loss in ALS. Altered expression of genes involved in copper handling indicated disrupted copper availability, and this was evident in decreased copper-dependent ferroxidase activity despite increased abundance of the ferroxidases ceruloplasmin and hephaestin. Mice expressing mutant SOD1 recapitulate salient features of ALS and the unsatiated requirement for copper in these mice is a biochemical target for CuII(atsm). Our results from human spinal cord indicate a therapeutic mechanism of action for CuII(atsm) involving copper availability may also be pertinent to sporadic cases of ALS.


Assuntos
Esclerose Amiotrófica Lateral , Complexos de Coordenação , Doenças Neurodegenerativas , Tiossemicarbazonas , Humanos , Camundongos , Animais , Cobre/metabolismo , Esclerose Amiotrófica Lateral/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Doenças Neurodegenerativas/metabolismo , Camundongos Transgênicos , Medula Espinal/metabolismo , Ceruloplasmina/metabolismo , Modelos Animais de Doenças
12.
Cell Mol Life Sci ; 81(1): 137, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478109

RESUMO

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.


Assuntos
Células Endoteliais , Traumatismos da Medula Espinal , Animais , Camundongos , Ratos , Barreira Hematoencefálica/metabolismo , Enzimas Desubiquitinantes/metabolismo , Células Endoteliais/metabolismo , Proteínas HMGB/metabolismo , Proteínas HMGB/farmacologia , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Fatores de Transcrição SOXF/genética , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
13.
Turk Neurosurg ; 34(2): 216-223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497173

RESUMO

AIM: To identify the predictive factors associated with the survival of patients with a diagnosis of primary spinal cord lymphoma (PSCL). MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used in this study, which involved 254 patients with PSCL. Data on the patients' age, sex, race, pathology, Ann Arbor stage, adjuvant therapy, and year of diagnosis were collected. Univariate and multivariate Cox regression models were conducted to detect the predictive variables. RESULTS: Of the 254 patients, 67 (26.4%) die from lymphoma at the time of data collection. Cancer-specific survival at 1, 3, and 5 years was 81.0%, 74.6%, and 74.1%, respectively. Diffuse large B-cell lymphoma (DLBL) was the highest prevalent histotype (n=140, 55.1%). The multivariate Cox regression models revealed that chemotherapy (hazard ratio (HR): 0.47; 95% confidence interval (CI), 0.16-0.82; p=0.040) and radiochemotherapy (HR: 0.43; 95% CI, 0.10-0.57; p=0.045) were independent predictors of favorable cancer-specific survival, whereas age - 80 years (HR: 6.51; 95% CI, 1.65-25.64; p=0.003) and DLBL (HR:1.71; 95% CI, 1.02-2.88; p=0.030) were independently associated with poor cancer-specific survival. CONCLUSION: The survival outcome of PSCL is favorable in the current treatment strategy. Chemotherapy and radiochemotherapy were predictors of favorable outcomes, whereas older age and DLBL were associated with poor prognosis.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Programa de SEER , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Modelos de Riscos Proporcionais , Medula Espinal/patologia
14.
Toxicol Appl Pharmacol ; 484: 116872, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428465

RESUMO

Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was used to construct an SCI rat model. The results indicated that the nuclear transfer factor-κB (NF-κB) pathway was identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and an inflammatory response was identified through the Gene Ontology (GO) enrichment analysis. Tumor necrosis factor (TNF) was identified as a crucial target. Western blotting revealed that TMP decreased the protein expression of TNF superfamily receptor 1 (TNFR1), inhibitor κB-α (IκB-α), and NF-κB p65 in spinal cord tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) demonstrated that TMP inhibited TNF-α, interleukin-1ß (IL-1ß), reactive oxygen species (ROS), and malondialdehyde (MDA) expression and enhanced superoxide dismutase (SOD) expression. Histopathological observation and behavior assessments showed that TMP improved morphology and motor function. In conclusion, TMP inhibits inflammatory response and oxidative stress, thereby exerting a neuroprotective effect that may be related to the regulation of the TNFR1/IκB-α/NF-κB p65 signaling pathway.


Assuntos
NF-kappa B , Pirazinas , Traumatismos da Medula Espinal , Animais , Ratos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa , Pirazinas/farmacologia , Ratos Sprague-Dawley , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/uso terapêutico , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/metabolismo
15.
FASEB J ; 38(6): e23563, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498358

RESUMO

Acute kidney injury (AKI), a prevalent clinical syndrome, involves the participation of the nervous system in neuroimmune regulation. However, the intricate molecular mechanism that governs renal function regulation by the central nervous system (CNS) is complex and remains incompletely understood. In the present study, we found that the upregulated expression of lncTCONS_00058568 in lower thoracic spinal cord significantly ameliorated AKI-induced renal tissue injury, kidney morphology, inflammation and apoptosis, and suppressed renal sympathetic nerve activity. Mechanistically, the purinergic ionotropic P2X7 receptor (P2X7R) was overexpressed in AKI rats, whereas lncTCONS_00058568 was able to suppress the upregulation of P2X7R. In addition, RNA sequencing data revealed differentially expressed genes associated with nervous system inflammatory responses after lncTCONS_00058568 was overexpressed in AKI rats. Finally, the overexpression of lncTCONS_00058568 inhibited the activation of PI3K/Akt and NF-κB signaling pathways in spinal cord. Taken together, the results from the present study show that lncTCONS_00058568 overexpression prevented renal injury probably by inhibiting sympathetic nerve activity mediated by P2X7R in the lower spinal cord subsequent to I/R-AKI.


Assuntos
Injúria Renal Aguda , Receptores Purinérgicos P2X7 , Ratos , Animais , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Injúria Renal Aguda/metabolismo , Medula Espinal/metabolismo
16.
Pain Physician ; 27(3): 161-168, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506683

RESUMO

BACKGROUND: Cervical transforaminal epidural steroid injections have become less popular due to the risk of catastrophic complications they pose. However, cervical nerve root blocks are useful for surgical planning in patients with cervical radicular pain syndromes. OBJECTIVES: Our aim was to find a method of performing cervical selective nerve root blocks that removed the risk of catastrophic complications. STUDY DESIGN: Retrospective case review. SETTING: Academic multidisciplinary spine center. METHODS: Among patients, 50 consecutive cases were retrospectively reviewed for immediate pain scores and follow-up results. In the intervention, a posterior approach using a curved blunt needle was employed for cervical selective nerve root blocks to minimize the risk of arterial injection. To measure the outcomes, we used quantitative pain severity scores and qualitative responses. RESULTS: This technique detailed in this study has a high immediate analgesic effect that can be used for diagnostic purposes. It is not known if this technique has prognostic value with respect to surgery. The prolonged response rate is about 50%, which is in line with other techniques. LIMITATIONS: This study had no control group. CONCLUSION(S): Cervical selective nerve root blocks using a curved blunt needle and a posterior approach are effective in selectively identifying nerves that cause clinical symptoms. This technique minimizes the risk of arterial or spinal cord impingement and therefore may be safer than transforaminal selective nerve root blocks.


Assuntos
Radiculopatia , Raízes Nervosas Espinhais , Humanos , Estudos Retrospectivos , Raízes Nervosas Espinhais/cirurgia , Medula Espinal , Radiculopatia/cirurgia , Dor
17.
Acta Neuropathol Commun ; 12(1): 45, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509621

RESUMO

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.


Assuntos
Substância Branca , Humanos , Substância Branca/metabolismo , Integrina beta1/metabolismo , Remodelação Vascular/fisiologia , Medula Espinal/metabolismo , Substância Cinzenta/metabolismo , Hipóxia/metabolismo
18.
J Cell Mol Med ; 28(7): e18240, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509741

RESUMO

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.


Assuntos
Eletroacupuntura , Ferroptose , Neuralgia , Humanos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Eletroacupuntura/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Neuralgia/metabolismo , Neurônios/metabolismo , Medula Espinal/metabolismo , Analgésicos
19.
BMC Neurosci ; 25(1): 20, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528450

RESUMO

INTRODUCTION: The optimum time to mobilise (standing, walking) following spinal cord injury (SCI) is unknown but may have implications for patient outcomes. There are no high-quality experimental studies that examine this issue, with a paucity of guidance for clinicians. Pre-clinical studies lead research in this field and can contribute to knowledge and support future clinical practice. OBJECTIVE: to evaluate the effect of early compared to no mobilisation on pathophysiological and functional outcomes in animals with induced SCI. METHODS: A systematic review with meta-analysis was conducted by searching pre-clinical literature in MEDLINE (PubMed), Embase (Ovid), Web of Science, OpenGrey, and EThOS (June 2023). Studies were included of any research method giving numerical results comparing pathophysiological and functional outcomes in rats and mice mobilised within 14-days of induced SCI to those that did not mobilise. Data were synthesised using random-effects meta-analyses. The quality of the evidence was assessed using the CAMARADES checklist. The certainty of findings was reported using the GRADE approach. This study is registered on PROSPERO (CRD42023437494). RESULTS: Seventeen studies met the inclusion criteria. Outcomes found that Brain Derived Neurotrophic Factor levels were greater in those that initiated mobilisation within 14-days of SCI compared to the groups that did not. Mobilisation initiated within 14-days of SCI was also associated with statistically significant functional gains: (Basso, Beattie and Bresnahan locomotor rating score (BBB) = 2.13(0-21), CI 1.43, 2.84, Ladder Rung Walking Task = - 12.38(0-100), CI 20.01, - 4.76). Meta-analysis identified the greatest functional gains when mobilisation was initiated within 3 days of SCI (BBB = 3.00, CI 2.31-3.69, p < 0.001), or when delivered at low intensity (BBB = 2.88, CI 2.03-3.70, p < 0.001). Confidence in the findings from this review was low to moderate due to the risk of bias and mixed methodological quality. CONCLUSION: Mobilisation instigated within 14-days of injury, may be an effective way of improving functional outcomes in animal models following SCI, with delays potentially detrimental to recovery. Outcomes from this study support further research in this field to guide future clinical practice.


Assuntos
Deambulação Precoce , Traumatismos da Medula Espinal , Humanos , Ratos , Camundongos , Animais , Recuperação de Função Fisiológica/fisiologia , Modelos Animais de Doenças , Medula Espinal
20.
CNS Neurosci Ther ; 30(3): e14593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38528832

RESUMO

BACKGROUND: Inflammation can worsen spinal cord injury (SCI), with dendritic cells (DCs) playing a crucial role in the inflammatory response. They mediate T lymphocyte differentiation, activate microglia, and release cytokines like NT-3. Moreover, DCs can promote neural stem cell survival and guide them toward neuron differentiation, positively impacting SCI outcomes. OBJECTIVE: This review aims to summarize the role of DCs in SCI-related inflammation and identify potential therapeutic targets for treating SCI. METHODS: Literature in PubMed and Web of Science was reviewed using critical terms related to DCs and SCI. RESULTS: The study indicates that DCs can activate microglia and astrocytes, promote T-cell differentiation, increase neurotrophin release at the injury site, and subsequently reduce secondary brain injury and enhance functional recovery in the spinal cord. CONCLUSIONS: This review highlights the repair mechanisms of DCs and their potential therapeutic potential for SCI.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal , Humanos , Medula Espinal , Microglia , Inflamação/complicações , Células Dendríticas
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