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1.
Medicine (Baltimore) ; 98(41): e17553, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593138

RESUMO

RATIONALE: Intraspinal anesthesia, the most common anesthesia type of orthopedic operation, is regarded as safe and simple. Despite of the rare incidence, puncture related complication of intraspinal anesthesia is catastrophic for spinal cord. Here we present an intradural hematoma case triggered by improper anesthesia puncture. The principal reason of this tragedy was rooted in the neglect of spine deformities diagnosis before anesthesia. To the best of our knowledge, there is no specific case report focusing on the intradural hematoma triggered by improper anesthesia puncture. PATIENT CONCERNS: Hereby a case of thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture was reported. The presenting complaint of the patient was little neurologic function improvement after surgery at 6-month follow-up. DIAGNOSES: Emergency MRI demonstrated that massive spindle-like intradural T2-weighted image hypointense signal masses from T12 to S2 badly compressed the dural sac ventrally, and his conus medullaris was at L3/4 intervertebral level with absence of L5 vertebral lamina. Hereby, the diagnoses were congenital spinal bifida, tethered cord syndrome, spine intradural hematoma, and paraplegia. INTERVENTIONS: Urgent surgical interventions including laminectomy, spinal canal exploration hematoma removal, and pedicle fixation were performed. The patient received both medication (mannitol, mecobalamin, and steroids) and rehabilitation (neuromuscular electric stimulation, hyperbaric oxygen). OUTCOMES: Postoperation, he had regained only hip and knee flexion at II grade strength. His neurologic function was unchanged until 3 weeks postoperation. Six-month follow-up showed just little neurologic function improvement, and the American Spinal Injury Association grade was C. LESSONS: By presenting an intradural hematoma case triggered by improper anesthesia puncture, we shared the treatment experience and discussed the potential mechanism of neurologic compromise. The principal reason for this tragedy is preanesthesia examination deficiency. Necessary radiology examinations must be performed to prevent misdiagnosis for spinal malformation.


Assuntos
Anestesia/efeitos adversos , Hematoma/etiologia , Punções/efeitos adversos , Adulto , Descompressão Cirúrgica/métodos , Diagnóstico Diferencial , Hematoma/diagnóstico por imagem , Hematoma/patologia , Hematoma/cirurgia , Humanos , Doença Iatrogênica/epidemiologia , Injeções Espinhais , Laminectomia/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Doenças da Medula Espinal/patologia , Coluna Vertebral/anormalidades , Coluna Vertebral/diagnóstico por imagem , Resultado do Tratamento
2.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 30(5): 233-237, sept.-oct. 2019. ilus
Artigo em Inglês | IBECS | ID: ibc-183877

RESUMO

Vertebral hemangiomas are relatively common, but those causing spinal cord compression are rare. A 19-year-old male presented with thoracic back pain. The neurologic examination was normal and radiological examinations demonstrated an aggressive vertebral hemangioma centered within the T11 vertebral body. Damaged vertebral bone and soft tissue components of the mass were observed in the epidural space. Surgery was performed using a new technique involving radiofrequency ablation, injection of a hemostatic agent (FLOSEAL, Baxter, USA), and bone autograft placement in the affected vertebral body. There were no complications intra- or postoperatively, and the patient's back pain resolved completely during the postsurgical period. Bleeding is a serious issue in cases of aggressive vertebral hemangioma. This new technique provides improved bleeding control and strengthens the affected vertebra through autograft placement


Los hemangiomas vertebrales son relativamente comunes, pero los que causan la compresión de la médula espinal son raros. Un hombre de 19 años presentó dolor de espalda torácica. El examen neurológico fue normal y los exámenes radiológicos demostraron un hemangioma vertebral agresivo centrado en el cuerpo vertebral T11. Se observaron componentes óseos y vertebrales dañados de la masa en el espacio epidural. La cirugía se realizó utilizando una nueva técnica que incluía ablación por radiofrecuencia, inyección de un agente hemostático (FLOSEAL, Baxter, EE. UU.) Y colocación de autoinjerto de hueso en el cuerpo vertebral afectado. No hubo complicaciones intra y postoperatorias, y el dolor de espalda del paciente se resolvió completamente durante el período posquirúrgico. El sangrado es un problema grave en los casos de hemangioma vertebral agresivo. Esta nueva técnica proporciona un mejor control de la hemorragia y fortalece la vértebra afectada a través de la colocación del autoinjerto


Assuntos
Humanos , Masculino , Adulto Jovem , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Ablação por Radiofrequência/métodos , Hemostáticos/administração & dosagem , Transplante Autólogo/métodos , Medula Espinal/patologia , Dor nas Costas/etiologia , Espaço Epidural/diagnóstico por imagem , Espaço Epidural/cirurgia
3.
Medicine (Baltimore) ; 98(42): e17591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626131

RESUMO

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a common complication of spinal surgery as well as thoracic and abdominal surgery. Acute cytotoxic edema is the key pathogenic alteration. Therefore, avoiding or decreasing cellular edema has become the major target for SCII treatment. METHODS: The antiedema activity of ginsenoside Rb1 on aquaporin (AQP) 4, nerve growth factor (NGF), and brain-derived neurotrophic factor expression was detected by western blot and real-time polymerase chain reaction under conditions of oxygen-glucose deprivation/reoxygenation (OGD/R) in a rat astrocyte model in vitro. In addition, the cellular membrane permeability of AQP4 overexpressing cells or AQP4 small interfering RNA-transfected cells was detected. RESULTS: Ginsenoside Rb1 significantly prevented OGD/R-induced AQP4 downregulation in rat astrocytes. In addition, ginsenoside Rb1 treatment or AQP4 overexpression in rat astrocytes significantly attenuated the OGD/R-induced increase of cellular membrane permeability. Moreover, ginsenoside Rb1 obviously prevented the OGD/R-induced decrease of NGF and BDNT expression in rat astrocytes. CONCLUSION: These findings demonstrate that ginsenoside Rb1 can relieve spinal cord edema and improve neurological function by increasing AQP4 expression.


Assuntos
Aquaporina 4/genética , Astrócitos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ginsenosídeos/farmacologia , Glucose/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Animais , Animais Recém-Nascidos , Aquaporina 4/biossíntese , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , RNA/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Medula Espinal/patologia
4.
Nat Neurosci ; 22(10): 1659-1668, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31501573

RESUMO

Neuropathic pain can be a debilitating condition with both sensory and affective components, the underlying brain circuitry of which remains poorly understood. In the present study, a basolateral amygdala (BLA)-prefrontal cortex (PFC)-periaqueductal gray (PAG)-spinal cord pathway was identified that is critical for the development of mechanical and thermal hypersensitivity after peripheral nerve injury. It was shown that nerve injury strengthens synaptic input from the BLA onto inhibitory interneurons located in the prelimbic medial PFC, by virtue of reduced endocannabinoid modulation. These augmented synaptic connections mediate a feedforward inhibition of projections from the PFC to the ventrolateral PAG region and its downstream targets. Optogenetic approaches combined with in vivo pharmacology reveal that these BLA-PFC-PAG connections alter pain behaviors by reducing descending noradrenergic and serotoninergic modulation of spinal pain signals. Thus, a long-range brain circuit was identified that is crucial for pain processing and that can potentially be exploited toward targeting neuropathic pain.


Assuntos
Vias Neurais/patologia , Neuralgia/patologia , Neurônios/patologia , Tonsila do Cerebelo/patologia , Animais , Comportamento Animal , Temperatura Alta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Neuralgia/psicologia , Optogenética , Substância Cinzenta Periaquedutal/patologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/psicologia , Estimulação Física , Córtex Pré-Frontal/patologia , Medula Espinal/patologia , Sinapses/patologia
5.
Medicine (Baltimore) ; 98(36): e16887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490372

RESUMO

RATIONALE: Multiple syphilitic gummas involving both the brain and spinal cord are quite rare. Central nervous system (CNS) syphilitic gummas are commonly misdiagnosed as CNS tumors, and clinical suspicion and diagnosis of a syphilitic gumma by physicians are vital to avoiding unnecessary surgeries. Our case emphasizes the importance of routine serologic syphilis tests and standard therapy with penicillin in patients with a CNS mass. PATIENT CONCERNS: A 22-year-old previously healthy man presented with a 9-day history of progressive right lower limb weakness. DIAGNOSIS: The diagnosis of gummatous neurosyphilis was based on positive serological, cerebrospinal fluid tests for syphilis and magnetic resonance imaging (MRI) findings, which revealed the presence of multiple dural-based enhancing masses with marked edema. INTERVENTIONS: Therapy consisting of intravenous penicillin G at 24 million units daily divided into 6 doses were given for a total of 21 days, along with 3 weekly intramuscular injections of benzathine penicillin G (2.4 million units) to ensure that the syphilitic lesions in the CNS were adequately treated. OUTCOMES: Complete resolution of the lesions was observed on MRI over a 3-month period. LESSONS: The importance of routine serologic syphilis tests and standard therapy with penicillin in patients with central CNS mass lesions is noted to avoiding unnecessary surgeries.


Assuntos
Neurossífilis/diagnóstico , Antibacterianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Diagnóstico Diferencial , Soronegatividade para HIV , Humanos , Imagem por Ressonância Magnética , Masculino , Neurossífilis/diagnóstico por imagem , Neurossífilis/tratamento farmacológico , Penicilina G/uso terapêutico , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Adulto Jovem
6.
Int. j. morphol ; 37(2): 428-437, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002239

RESUMO

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.


El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.


Assuntos
Animais , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia do Cordão Espinal/tratamento farmacológico , Melatonina/administração & dosagem , Antioxidantes/administração & dosagem , Paraplegia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Dinoprostona/sangue , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/farmacologia , Melatonina/farmacologia , Nitritos/sangue , Antioxidantes/farmacologia
8.
BMC Vet Res ; 15(1): 175, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138270

RESUMO

BACKGROUND: Dourine, a venereal transmitted trypanosomosis caused by Trypanosoma equiperdum, has different clinical signs related to the reproductive and nervous system. Pathologic tissue changes associated with the disease are poorly described. The present study describes the histopathological lesions in naturally T. equiperdum-infected horses in the chronical stage of dourine. RESULTS: Four chronically dourine diseased horses underwent a post-mortem examination. They were Woo test negative, but CATT/T. evansi positive, had a low packed cell volume (PCV) and exhibited obvious clinical signs of dourine. Post-mortem examination did not reveal gross lesions in the organs assumed to be responsible for the symptomatology. On histopathology, genital organs were affected, with mononuclear cell infiltration and erosions and degeneration of seminiferous tubules and perivascular lymphoplasmacytic cuffing in the uterus. In the nervous system, mononuclear cell infiltration was located in peripheral nerves, ganglia and in the spinal cord, leading to axonal degeneration. Real-time PCR using ITS primer revealed the presence of trypanosomes in these organs and conventional PCRs using maxicircle and RoTat1.2 primers further confirmed the involvement of T. equiperdum since the DNAs from the vagina, testicle, distal spinal cord, sciatic and obturator nerves found to be positive for maxicircle and negative for RoTat 1.2. CONCLUSIONS: The histopathological lesions in the spinal cord and peripheral nerves explain the incoordination of the hind legs in T. equiperdum-infected horses, whilst its presence in the genital tract exemplifies the venereal transmission.


Assuntos
Mal do Coito (Veterinária)/patologia , Doenças dos Cavalos/parasitologia , Infecções do Sistema Genital/veterinária , Animais , Mal do Coito (Veterinária)/parasitologia , Feminino , Doenças dos Cavalos/patologia , Cavalos , Masculino , Doenças do Sistema Nervoso Periférico/parasitologia , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/veterinária , Reação em Cadeia da Polimerase , Infecções do Sistema Genital/parasitologia , Infecções do Sistema Genital/patologia , Túbulos Seminíferos/parasitologia , Túbulos Seminíferos/patologia , Medula Espinal/parasitologia , Medula Espinal/patologia , Trypanosoma/isolamento & purificação , Útero/parasitologia , Útero/patologia
9.
J Vet Med Sci ; 81(7): 986-989, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31092762

RESUMO

Atypical scrapie in goats has only been reported in European countries. The present study reports the identification of the first case of atypical scrapie in goats in Japan. The genotype of the animal was ALRQ/ALHQ at codons 136, 141, 154, and 171 in prion protein (PrP). Western blot analysis showed a multiplex proteinase K-resistant prion protein (PrP-res) band pattern with a band <15 kDa that was clearly distinguishable from the triplet PrP-res band pattern observed in classical scrapie cases. Histopathological and immunohistological examination showed mild vacuolation and fine granular to globular immunolabelling of disease-associated PrP in the dorsal horn of cervical spinal cord. Collectively, our results confirmed that this goat was affected by atypical scrapie.


Assuntos
Doenças das Cabras/diagnóstico , Scrapie/diagnóstico , Animais , Western Blotting/veterinária , Feminino , Genótipo , Doenças das Cabras/patologia , Cabras , Japão , Proteínas Priônicas/genética , Scrapie/patologia , Medula Espinal/patologia
10.
J Clin Neurosci ; 65: 34-40, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053399

RESUMO

Pediatric patients presenting with intramedullary spinal cord lesions often require specific diagnoses to guide their treatment plans. Though results from magnetic resonance imaging and lumbar puncture may narrow the differential diagnosis, these tests cannot always provide a definitive diagnosis. In such cases, spinal cord biopsy may be undertaken to provide a specific histopathologic diagnosis for guiding treatment. Data from the adult population show 24% of spinal cord biopsies can be nondiagnostic and the procedure may carry a 21% complication rate. Therefore, spinal cord biopsy may portend a similar high risk-to-benefit ratio in the pediatric population. Here, we review spinal cord biopsy cases scheduled for diagnosis, and not debulking, at a high volume pediatric referral center during a seventeen-year period. We report our experience with five patients who met our inclusion criteria. Due to the rarity of the procedure, statistically significant factors associated with improved diagnostic yield or peri-operative complication could not be identified. A definitive diagnosis which guided the post-operative treatment plan was obtained in four of our five patients. None of our patients developed post-operative motor deficits. However, these patients were susceptible to the same risks of open spine surgery, such as wound infections and spinal deformities. Our case series shows that intramedullary spinal cord biopsies may provide tissue for obtaining histopatholgic diagnoses. However, the potential risks of complication, and the possibility of obtaining nondiagnostic tissue, should be discussed with patients, families and their medical treatment teams.


Assuntos
Biópsia , Doenças da Medula Espinal/diagnóstico , Adolescente , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Estudos Retrospectivos , Medula Espinal/patologia , Neoplasias da Medula Espinal/diagnóstico
11.
Cell Mol Life Sci ; 76(21): 4355-4368, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31041455

RESUMO

Axons in the central nervous system (CNS) typically fail to regenerate after injury. This failure is multi-factorial and caused in part by disruption of the axonal cytoskeleton. The cytoskeleton, in particular microtubules (MT), plays a critical role in axonal transport and axon growth during development. In this regard, members of the kinesin superfamily of proteins (KIFs) regulate the extension of primary axons toward their targets and control the growth of collateral branches. KIF2A negatively regulates axon growth through MT depolymerization. Using three different injury models to induce SCI in adult rats, we examined the temporal and cellular expression of KIF2A in the injured spinal cord. We observed a progressive increase of KIF2A expression with maximal levels at 10 days to 8 weeks post-injury as determined by Western blot analysis. KIF2A immunoreactivity was present in axons, spinal neurons and mature oligodendrocytes adjacent to the injury site. Results from the present study suggest that KIF2A at the injured axonal tips may contribute to neurite outgrowth inhibition after injury, and that its increased expression in inhibitory spinal neurons adjacent to the injury site might contribute to an intrinsic wiring-control mechanism associated with neuropathic pain. Further studies will determine whether KIF2A may be a potential target for the development of regeneration-promoting or pain-preventing therapies.


Assuntos
Cinesina/análise , Cinesina/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Modelos Animais de Doenças , Cinesina/genética , Masculino , Regeneração Nervosa/genética , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia
14.
J Neuroinflammation ; 16(1): 82, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975169

RESUMO

BACKGROUND: Neuropathic pain is caused by sensory nerve injury, but effective treatments are currently lacking. Microglia are activated in the spinal dorsal horn after sensory nerve injury and contribute to neuropathic pain. Accordingly, molecules expressed by these cells are considered potential targets for therapeutic strategies. Our previous gene screening study using a mouse model of motor nerve injury showed that the G-protein-coupled receptor 34 gene (GPR34) is induced by nerve injury. Because GPR34 is now considered a microglia-enriched gene, we explored the possibility that it might be involved in microglial activation in the dorsal horn in a mouse model of neuropathic pain. METHODS: mRNA expression of GPR34 and pro-inflammatory molecules was determined by quantitative real-time PCR in wild-type and GPR34-deficient mice with L4 spinal nerve injury. In situ hybridization was used to identify GPR34 expression in microglia, and immunohistochemistry with the microglial marker Iba1 was performed to examine microglial numbers and morphology. Mechanical sensitivity was evaluated by the von Frey hair test. Liquid chromatography-tandem mass spectrometry quantified expression of the ligand for GPR34, lysophosphatidylserine (LysoPS), in the dorsal horn, and a GPR34 antagonist was intrathecally administrated to examine the effect of inhibiting LysoPS-GPR34 signaling on mechanical sensitivity. RESULTS: GPR34 was predominantly expressed by microglia in the dorsal horn after L4 nerve injury. There were no histological differences in microglial numbers or morphology between WT and GPR34-deficient mice. However, nerve injury-induced pro-inflammatory cytokine expression levels in microglia and pain behaviors were significantly attenuated in GPR34-deficient mice. Furthermore, the intrathecal administration of the GPR34 antagonist reduced neuropathic pain. CONCLUSIONS: Inhibition of GPR34-mediated signal by GPR34 gene deletion reduced nerve injury-induced neuropathic pain by suppressing pro-inflammatory responses of microglia without affecting their morphology. Therefore, the suppression of GPR34 activity may have therapeutic potential for alleviating neuropathic pain.


Assuntos
Microglia/metabolismo , Neuralgia/metabolismo , Neuralgia/patologia , Receptores de Lisofosfolipídeos/metabolismo , Medula Espinal/patologia , Análise de Variância , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Fatores Reguladores de Interferon/metabolismo , Lisofosfolipídeos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Neuralgia/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Medição da Dor , Limiar da Dor/fisiologia , Proteína Quinase C/metabolismo , RNA Mensageiro/metabolismo , Receptores de Lisofosfolipídeos/antagonistas & inibidores , Receptores de Lisofosfolipídeos/genética , Fatores de Tempo
15.
Mediators Inflamm ; 2019: 4856156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001066

RESUMO

Diabetic neuropathic pain (DNP) is a common and serious complication of diabetic patients. The pathogenesis of DNP is largely unclear. The proinflammation proteins, CXCR4, and TNF-α play critical roles in the development of pain, while their relative roles in the development of DNP and especially its progression is unknown. We proposed that establishment of diabetic pain models in rodents and evaluating the stability of behavioral tests are necessary approaches to better understand the mechanism of DNP. In this study, Von Frey and Hargreaves Apparatus was used to analyze the behavioral changes of mechanical allodynia and heat hyperalgesia in streptozotocin-induced diabetic rats at different phases of diabetes. Moreover, CXCR4 and TNF-α of spinal cord dorsal and dorsal root ganglia (DRG) were detected by western blotting and immunostaining over time. The values of paw withdrawal threshold (PWT) and paw withdrawal latencies (PWL) were reduced as early as 1 week in diabetic rats and persistently maintained at lower levels during the progression of diabetes as compared to control rats that were concomitant with significant increases of both CXCR4 and TNF-α protein expressions in the DRG at 2 weeks and 5 weeks (the end of the experiments) of diabetes. By contrast, CXCR4 and TNF-α in the spinal cord dorsal horn did not significantly increase at 2 weeks of diabetes while both were significantly upregulated at 5 weeks of diabetes. The results indicate that central sensitization of spinal cord dorsal may result from persistent peripheral sensitization and suggest a potential reference for further treatment of DNP.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Neuropatias Diabéticas/patologia , Gânglios Espinais/metabolismo , Receptores CXCR4/metabolismo , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Ratos , Transdução de Sinais/fisiologia , Medula Espinal/patologia
16.
Ann Clin Lab Sci ; 49(2): 265-270, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31028074

RESUMO

BACKGROUND: Spinal neurosyphilis manifesting as a solitary syphilitic gumma is exceedingly rare. There are non-specific imaging findings and challenges in the diagnosis of spinal syphilitic gumma, which could be easily misdiagnosed as tumor lesions and require surgical resection or biopsy. CLINICAL PRESENTATION: We report the case of a 45-year-old female patient who was diagnosed with Spinal syphilitic gumma. Our case is the first reported case of spinal cord syphilitic gumma with intradural-extramedullary and intramedullary involvement. CONCLUSION: Spinal syphilitic gumma exhibits diverse clinical manifestations, lacks specific imaging features, accompanied by the patient's history deliberately concealed. Since clinicians do not have sufficient knowledge about such rare cases, misdiagnosis and missed diagnosis will be likely. When there is clinical suspicion for spinal syphilitic gumma, clinicians should pay close attention to relevant medical history, carry out a comprehensive physical examination and specific serological tests and cerebrospinal fluid (CSF) analysis. In summary, in cases with stable neurologic conditions, a trial administration of intravenous penicillin with follow-up imaging may be the optimal treatment option, and in cases with rapid progression or acute exacerbation, a surgical resection together with systemic antibiotic treatment for syphilis after surgery may be the best treatment strategy.


Assuntos
Síndrome de Brown-Séquard/complicações , Neurossífilis/complicações , Medula Espinal/patologia , Adulto , Idoso , Síndrome de Brown-Séquard/diagnóstico por imagem , Feminino , Humanos , Inflamação/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurossífilis/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Resultado do Tratamento
17.
Nat Neurosci ; 22(6): 887-896, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31011226

RESUMO

Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression of Bsn in flies resulted in reduction of lifespan, while genetic disruption of Bsn protected mice from inflammation-induced neuroaxonal injury. Notably, pharmacological proteasome activation boosted the clearance of accumulated Bsn and enhanced neuronal survival. Our study demonstrates that neuroinflammation initiates toxic protein accumulation in neuronal somata and advocates proteasome activation as a potential remedy.


Assuntos
Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Drosophila , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia
18.
Science ; 364(6435): 89-93, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30948552

RESUMO

Paralysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify pathway dynamics, distinguish regional differences between microglia and astrocyte populations at early time points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.


Assuntos
Esclerose Amiotrófica Lateral/genética , Expressão Gênica , Neurônios Motores/metabolismo , Medula Espinal/metabolismo , Esclerose Amiotrófica Lateral/patologia , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Microglia/metabolismo , Microglia/patologia , Neurônios Motores/patologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Degeneração Neural/genética , Degeneração Neural/fisiopatologia , Neuroglia/metabolismo , Neuroglia/patologia , Mudanças Depois da Morte , Análise Espaço-Temporal , Medula Espinal/patologia , Transcriptoma
19.
J Vet Sci ; 20(2): e7, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30944530

RESUMO

The magnetic resonance (MR) features of spinal epidural hemorrhage depending with the passage of time have a meaning in veterinary medicine. The aim of this study is to propose the characteristic MR image of spinal epidural hemorrhage using a lower field permanent magnet scanner in dogs. A total of 8 clinically normal beagle dogs, weighing about 9 kg, were allocated. After a baseline MR examination, spinal epidural hemorrhage was created. MR scanning was executed on days 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 using 0.25 Tesla low field MR. Transverse MR images were attained for image examination. T2W, T1W, fluid-attenuated inversion recovery (FLAIR), short tau inversion recovery (STIR), and T2*-GRE sequences were used. Images were compared subjectively for signal transition assessment. Spinal epidural hemorrhage models were produced positively in 8 dogs at the T12 to L2 region. Initially, the spinal cord and epidural lesions were hyper-intense on T2W and T1W images. On T2W, FLAIR and STIR images, the spinal cord lesion was steadily hyperintense. No significant and consistent hypointense signal indicating hemorrhage was seen on T2*-GRE images. This study result suggests that relatively consistent hyperinstensity on T2 and FLAIR is observed for 30 days, meanwhile T2*-GRE imaging is less useful in hemorrhage detection.


Assuntos
Doenças do Cão/diagnóstico por imagem , Hematoma Epidural Espinal/veterinária , Imagem por Ressonância Magnética/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Hematoma Epidural Espinal/diagnóstico por imagem , Hematoma Epidural Espinal/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Fatores de Tempo
20.
Int J Mol Sci ; 20(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959793

RESUMO

Theiler's murine encephalomyelitis (TME) represents a versatile animal model for studying the pathogenesis of demyelinating diseases such as multiple sclerosis. Hallmarks of TME are demyelination, astrogliosis, as well as inflammation. Previous studies showed that matrix metalloproteinase 12 knockout (Mmp12-/-) mice display an ameliorated clinical course associated with reduced demyelination. The present study aims to elucidate the impact of MMP12 deficiency in TME with special emphasis on astrogliosis, macrophages infiltrating the central nervous system (CNS), and the phenotype of microglia/macrophages (M1 or M2). SJL wild-type and Mmp12-/- mice were infected with TME virus (TMEV) or vehicle (mock) and euthanized at 28 and 98 days post infection (dpi). Immunohistochemistry or immunofluorescence of cervical and thoracic spinal cord for detecting glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), chemokine receptor 2 (CCR2), CD107b, CD16/32, and arginase I was performed and quantitatively evaluated. Statistical analyses included the Kruskal⁻Wallis test followed by Mann⁻Whitney U post hoc tests. TMEV-infected Mmp12-/- mice showed transiently reduced astrogliosis in association with a strong trend (p = 0.051) for a reduced density of activated/reactive microglia/macrophages compared with wild-type mice at 28 dpi. As astrocytes are an important source of cytokine production, including proinflammatory cytokines triggering or activating phagocytes, the origin of intralesional microglia/macrophages as well as their phenotype were determined. Only few phagocytes in wild-type and Mmp12-/- mice expressed CCR2, indicating that the majority of phagocytes are represented by microglia. In parallel to the reduced density of activated/reactive microglia at 98 dpi, TMEV-infected Mmp12-/- showed a trend (p = 0.073) for a reduced density of M1 (CD16/32- and CD107b-positive) microglia, while no difference regarding the density of M2 (arginase I- and CD107b-positive) cells was observed. However, a dominance of M1 cells was detected in the spinal cord of TMEV-infected mice at all time points. Reduced astrogliosis in Mmp12-/- mice was associated with a reduced density of activated/reactive microglia and a trend for a reduced density of M1 cells. This indicates that MMP12 plays an important role in microglia activation, polarization, and migration as well as astrogliosis and microglia/astrocyte interaction.


Assuntos
Astrócitos/patologia , Infecções por Cardiovirus/enzimologia , Infecções por Cardiovirus/virologia , Gliose/enzimologia , Gliose/virologia , Metaloproteinase 12 da Matriz/deficiência , Microglia/patologia , Medula Espinal/patologia , Animais , Movimento Celular , Proteína Glial Fibrilar Ácida/metabolismo , Imunofenotipagem , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Camundongos Knockout , Fenótipo
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