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1.
Nat Commun ; 12(1): 3251, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059686

RESUMO

ALS is characterized by progressive inability to execute movements. Motor neurons innervating fast-twitch muscle-fibers preferentially degenerate. The reason for this differential vulnerability and its consequences on motor output is not known. Here, we uncover that fast motor neurons receive stronger inhibitory synaptic inputs than slow motor neurons, and disease progression in the SOD1G93A mouse model leads to specific loss of inhibitory synapses onto fast motor neurons. Inhibitory V1 interneurons show similar innervation pattern and loss of synapses. Moreover, from postnatal day 63, there is a loss of V1 interneurons in the SOD1G93A mouse. The V1 interneuron degeneration appears before motor neuron death and is paralleled by the development of a specific locomotor deficit affecting speed and limb coordination. This distinct ALS-induced locomotor deficit is phenocopied in wild-type mice but not in SOD1G93A mice after appearing of the locomotor phenotype when V1 spinal interneurons are silenced. Our study identifies a potential source of non-autonomous motor neuronal vulnerability in ALS and links ALS-induced changes in locomotor phenotype to inhibitory V1-interneurons.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Interneurônios/patologia , Locomoção/fisiologia , Neurônios Motores/patologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Animais , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fibras Musculares de Contração Rápida/fisiologia , Junção Neuromuscular/patologia , Junção Neuromuscular/fisiopatologia , Medula Espinal/citologia , Superóxido Dismutase/genética , Superóxido Dismutase-1/genética
2.
Zhen Ci Yan Jiu ; 46(5): 375-9, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085459

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) and "Huiyang" (BL35) on the expression of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and cellular oncogene fos (c-fos) phosphorylated of spinal dorsal horn in rats with interstitial cystitis (IC). METHODS: Eighteen female Wistar rats were randomly divided into control, model and EA groups, with 6 rats in each group. The IC model was established by intraperitoneal injection of cyclophosphamide (150 mg/kg). EA (30 Hz, 1 mA) was applied to bilateral BL32 and BL35 for 20 min, once daily for 3 consecutive days. The bladder pain was measured by using a Von Frey at 48 h after modeling and 24 h after EA. The expression levels of p-ERK1/2 and c-fos protein in L6-S1 segment of spinal cord were detected by Western blot, and the expression of p-ERK1/2 and c-fos in the right spinal dorsal horn were displayed by immunofluorescence staining. RESULTS: After modeling, the bladder mechanical pain threshold (PT) was significantly decreased (P<0.05), the protein expression of p-ERK1/2 and c-fos in the spinal cord was increased (P<0.05) and the immunofluorescence surface density of p-ERK1/2 and c-fos in the right dorsal horn of spinal cord was increased (P<0.05) in the model group relevant to the control group. After EA intervention, IC-induced reduction of PT, and increases of the expression of p-ERK1/2 and c-fos as well as immunofluorescence surface density of p-ERK1/2 and c-fos were reversed in the EA group relevant to the model group (P<0.05). CONCLUSION: EA at BL 32 and BL 35 has an analgesic effect in IC rats, which may be related to its effect in down-regulating the expression of p-ERK1/2 and c-fos in spinal dorsal horn.


Assuntos
Cistite Intersticial , Eletroacupuntura , Animais , Feminino , Sistema de Sinalização das MAP Quinases , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo
3.
No Shinkei Geka ; 49(3): 665-676, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34092573

RESUMO

In this paper, we outlined the diagnostic and treatment strategies for spinal arteriovenous malformations, focusing on dural and perimedullary arteriovenous fistula(AVF). In many patients with spinal arteriovenous malformations, the symptoms are non-specific. Therefore, we consider it is critical to detect the signal flow voids in the enlarged spinal veins using MRI. An accurate understanding of the vascular structures is indispensable for deciding appropriate treatment strategies. Hence, performing an angiography is essential. Regarding treatment, whether to select surgical or endovascular treatment for AVF depends largely on the institution's protocols. However, the treatment should always be based on an accurate diagnosis.


Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Malformações Vasculares do Sistema Nervoso Central , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/cirurgia , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Humanos , Imageamento por Ressonância Magnética , Medula Espinal/cirurgia
4.
Radiologe ; 61(6): 575-585, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-34105011

RESUMO

Autoimmune inflammatory diseases of the central nervous system (CNS) can be a diagnostic challenge despite advanced imaging techniques. Diagnostic errors can have fatal consequences (e. g. tumefactive lesions) as inappropriate treatment can exacerbate the symptoms of the patients. The aim of this article is to provide help in decision making for selected autoimmune inflammatory diseases of the CNS, in order not to fall into diagnostic traps. The primary focus is on lesions in the neurocranium as inflammatory diseases of the spinal cord were already extensively discussed in a previous article.


Assuntos
Doenças do Sistema Nervoso Central , Esclerose Múltipla , Neuromielite Óptica , Sistema Nervoso Central , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Medula Espinal , Síndrome
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(5): 694-701, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34134956

RESUMO

OBJECTIVE: To investigate the effect of orexin-A on the functionality of ionotropic γ-aminobutyric acid (GABA) receptors in spinal cord ventral horn neurons and its mechanisms. OBJECTIVE: The spinal cord containing the lumbosacral enlargement was isolated from neonatal SD rats (7-12 days old) and sliced. The slices were digested with papain (in 0.18 g/30 mL artificial cerebrospinal fluid) for 40-60 min, and the ventral horn neurons were separated acutely using fire-polished Pasteur pipettes. After the cells adhered to the bottom of Petri dishes, patch-clamp experiments combined with pharmacological methods were performed to test the effects of orexin-A on GABA currents of the neurons treated with SB334867 (a selective OX1R antagonist), TCSOX229 (a selective OX2R antagonist), Bis-Ⅳ (a PKC inhibitor), PMA (a PKC agonist), Rp-cAMP (a PKA inhibitor), or BAPTA (Ca2+ chelator). OBJECTIVE: The isolated neurons maintained good morphologies with diverse shapes of cell body and long protrusions. Treatment with orexin-A significantly inhibited the amplitude of GABA-induced current (P < 0.001, n=49) with an inhibition rate of (67.48±12.50)%. SB334867 and TCSOX229, when applied simultaneously, completely abolished the suppressive effect of orexin-A on the GABA currents (P=0.93, n=6), and their separate use partially relieved the suppressive effect of orexin-A (P=0.001, n=8; P=0.02, n=8). The application of Bis-Ⅳ also abolished the suppressive effect of orexin-A on GABA currents (P=0.31, n=5). PMA mimicked the effect of orexin-A in these neurons and significantly inhibited GABA currents with an inhibition rate of (60.79±10.94)%, and the application of orexin-A did not cause further suppression of GABA currents in PMA-treated neurons (P=0.15, n=6). Orexin-A was still capable of suppressing GABA currents in Rp-cAMP-treated neurons (P=0.001, n=5). The extracellular Ca2+-free solution (P=0.004, n=8) or the presence of BAPTA (P=0.04, n=7) did not significantly affect the inhibitory effect of orexin-A on GABA currents. OBJECTIVE: Orexin-A inhibits GABA currents in the ventral horn neurons of rat spinal cord probably by activating OX1R, OX2R and Ca2+-independent PKC.


Assuntos
Células do Corno Anterior , Ácido gama-Aminobutírico , Animais , Animais Recém-Nascidos , Neurônios , Orexinas/farmacologia , Técnicas de Patch-Clamp , Proteína Quinase C , Ratos , Ratos Sprague-Dawley , Medula Espinal , Ácido gama-Aminobutírico/farmacologia
6.
J Pak Med Assoc ; 71(4): 1290-1291, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34125794

RESUMO

Spinal subdural haematoma (SSDH) is very rare but potentially life debilitating spinal vascular condition, often developing acutely. Usually managed conservatively but may require immediate evacuation to prevent potential harm to the spinal cord. Predisposing factors can be spontaneous or iatrogenic. MRI remains the modality of choice to diagnose and see the age and extent of haemorrhage. We hereby present the case of a young child who developed iatrogenic spinal subdural haematoma.


Assuntos
Hematoma Subdural Espinal , Criança , Hematoma Subdural Espinal/diagnóstico por imagem , Hematoma Subdural Espinal/etiologia , Hematoma Subdural Espinal/cirurgia , Humanos , Doença Iatrogênica , Imageamento por Ressonância Magnética , Medula Espinal
7.
Brain Nerve ; 73(6): 685-696, 2021 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-34127565

RESUMO

Spinal dural arteriovenous fistulas (SDAVF) are rare and most commonly affect men aged >50 years. Patients with SDAVF develop an abnormal vascular dural shunt between the dural branch of a segmental artery and a subdural radicular vein that drains the perimedullary venous system, leading to venous hypertension and secondary congestive myelopathy. Most SDAVFs are located in the thoracolumbar region, and usually patients present with slowly progressive paraparesis and urinary disturbances. SDAVF is diagnostically challenging; this condition may be misdiagnosed as lumbar spinal stenosis or myelitis. Clinicians should be aware of fluctuating symptoms in the early stages to avoid misdiagnosis of SDAVF. Claudication is associated with various activities including walking, bathing, drinking, and singing. On T2-weighted magnetic resonance imaging of the spinal cord, SDAVFs show a high signal intensity with a low signal intensity peripherally and dilated spinal cord veins in the subarachnoid space.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Doenças da Medula Espinal , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Diagnóstico Precoce , Humanos , Imageamento por Ressonância Magnética , Masculino , Medula Espinal
8.
Brain Nerve ; 73(6): 697-714, 2021 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-34127566

RESUMO

The cauda equina itself is an unsuitable site for radiological diagnostic imaging because the cauda equina is anatomically a small structure, and magnetic resonance imaging is of limited value to accurately detect lesions in this area. Therefore, in addition to the imaging findings of the cauda equina itself, it is necessary to consider findings in the spinal cord and other areas, as well as clinically correlate these data. In this article, we discuss diseases that cause cauda equina disorders and describe the characteristic imaging findings in such cases.


Assuntos
Cauda Equina , Cauda Equina/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Medula Espinal
9.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064332

RESUMO

Spinal cord injury (SCI) leads to numerous chronic and debilitating functional deficits that greatly affect quality of life. While many pharmacological interventions have been explored, the current unsurpassed therapy for most SCI sequalae is exercise. Exercise has an expansive influence on peripheral health and function, and by activating the relevant neural pathways, exercise also ameliorates numerous disorders of the central nervous system (CNS). While the exact mechanisms by which this occurs are still being delineated, major strides have been made in the past decade to understand the molecular underpinnings of this essential treatment. Exercise rapidly and prominently affects dendritic sprouting, synaptic connections, neurotransmitter production and regulation, and ionic homeostasis, with recent literature implicating an exercise-induced increase in neurotrophins as the cornerstone that binds many of these effects together. The field encompasses vast complexity, and as the data accumulate, disentangling these molecular pathways and how they interact will facilitate the optimization of intervention strategies and improve quality of life for individuals affected by SCI. This review describes the known molecular effects of exercise and how they alter the CNS to pacify the injury environment, increase neuronal survival and regeneration, restore normal neural excitability, create new functional circuits, and ultimately improve motor function following SCI.


Assuntos
Exercício Físico , Regulação da Expressão Gênica , Regeneração Nervosa/genética , Plasticidade Neuronal/genética , Recuperação de Função Fisiológica/genética , Traumatismos da Medula Espinal/genética , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Qualidade de Vida , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação , Simportadores/genética , Simportadores/metabolismo
11.
Ideggyogy Sz ; 74(5-6): 207-210, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34106547

RESUMO

Background and purpose: Fibrocartilaginous embolism is a rare cause of ischemic myelopathy. Authors report a case of a 39-year-old woman with progressive tetraparesis and severe autonomic dysfunction. Despite of the detailed examinations, the definite diagnosis was verified by autopsy. Methods: The patient was admitted because of progressive pain and numbness of the upper extremities and tetraparesis. Hypotonic muscles of the lower extremities with mild tetraparesis were observed. Magnetic resonance imaging showed an intramedullary lesion at the level of the cervical V-VII vertebral. Patient's tetraparesis worsened gradually to plegia with urinary retention. Expansive, rapidly progressing multiple decubiti developed, which were resistant to therapy. In spite of the complex therapy, the patient died. Results: No internal disease was found to explain the death by autopsy. Multiple subacute infarctions of the cervical myelon (involving the lateral columns as well) in the territory of the anterior spinal artery were verified by neuropathological examination. The occluded vessels were filled by a material containing cartilaginous cells, while signs of atherosclerosis or thrombosis were not present. Conclusion: Cartilaginous embolism of spinal arteries was diagnosed.


Assuntos
Doenças das Cartilagens , Embolia , Doenças da Medula Espinal , Adulto , Doenças das Cartilagens/complicações , Embolia/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Medula Espinal , Doenças da Medula Espinal/complicações
12.
BMJ Case Rep ; 14(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011645

RESUMO

Transverse myelitis is an inflammatory disease of the central nervous system that disrupts nerve signals' conduction. The illness is characterised by weakness in the lower limbs accompanied by paresthesia and urinary and bowel incontinence. The most disabling sequel is the onset of chronic neuropathic pain, which can severely limit the patient's independence and negatively affect her quality of life. We present the case of a patient who received a spinal neurostimulator after a failure of conventional medical treatment. Masking pain through paresthesia, a mechanism provided by the device significantly reduces pain perception. The treatment success in our patient represents an advance in pain therapy.


Assuntos
Terapia por Estimulação Elétrica , Mielite Transversa , Neuralgia , Feminino , Humanos , Mielite Transversa/complicações , Mielite Transversa/terapia , Neuralgia/etiologia , Neuralgia/terapia , Qualidade de Vida , Medula Espinal
13.
J Int Med Res ; 49(5): 3000605211005954, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34024183

RESUMO

There are limited treatment options for patients with foot drop and associated lower back and/or leg pain. We present a case series of three patients who received permanent implantation of 10 kHz spinal cord stimulation (10 kHz SCS) devices. Following treatment, all patients reported sustained improvements in lower back and leg pain, foot mechanics and function which resulted in increased mobility and cessation of opioid use for pain management. Patients were followed up for approximately four years. Treatment with 10 kHz SCS may be a promising alternative to other interventional procedures commonly used for these patients.


Assuntos
Dor Crônica , Neuropatias Fibulares , Estimulação da Medula Espinal , Humanos , Perna (Membro) , Manejo da Dor , Medula Espinal , Resultado do Tratamento
14.
Zhen Ci Yan Jiu ; 46(4): 259-65, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33931988

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture(EA)on locomotor activity and the expression of high-mobility group box-1(HMGB1) and Toll-like receptor 4(TLR4) in mice with spinal cord injury(SCI), so as to explore its mechanisms underlying improvement of SCI at the acute stage. METHODS: Forty-eight female C57BL/6 mice were equally randomized into 3 groups: sham operation, model and EA. The SCI model was established by clamping the spinal cord with a serrefine after laminectomy at the 1st lumbar vertebra(L1). EA (1.5 Hz/7.5 Hz, 1.0 mA) was applied to "Jiaji"(EXH-B2) for 10 min, once a day for 5 and 14 days, separately. The hindlimb locomotor function was assessed by Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB). Histopathological changes of the injured area of the spinal cord were determined by H.E. staining. The expression levels of spinal HMGB1, TLR4, ionized calcium binding adaptor molecule 1(Iba1) proteins were detected by Western blot, and the Iba1-positive microglial cells and HMGB1 and Iba1 co-labelled microglia were displayed by immunofluorescence staining. RESULTS: After SCI, the BBB scores on day 5 and 14 were obviously decreased (P<0.05), and the expression of HMGB1 on day 14, TLR4 on day 5 and 14, the number of Iba1-positive microglia as well as the co-expressed HMGB1/Iba1-positive microglia on day 5 and 14 were significantly increased in the model group relevant to the sham operation group (P<0.05, P<0.01). In the EA intervention group, SCI-induced reduction of BBB scores on day 5 and 14, and increases of the expression of HMGB1 and Iba1 on day 14, and TLR4 on day 5 and 14, and the number of Iba1-positive cells as well as the co-expressed HMGB1/Iba1-positive microglia on day 14 were reversed relevant to the model group (P<0.05,P<0.01). H.E. staining showed a structural disorder with lots of cavities, severe inflammatory infiltration with a large quantity of inflammatory cells, and a reduction of normal neurons in the injured spinal cord tissue in the model group, which was relatively milder, with lower activation of microglia in the EA group. CONCLUSION: EA can significantly improve locomotor function in SCI mice, which is associated with its effects in suppressing the expression of inflammatory factors such as HMGB1, TLR4, Iba1 and the over-activation of microglia.


Assuntos
Eletroacupuntura , Proteína HMGB1 , Traumatismos da Medula Espinal , Animais , Feminino , Proteína HMGB1/genética , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Coluna Vertebral , Receptor 4 Toll-Like/genética
15.
BMJ Case Rep ; 14(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975851

RESUMO

A 62-year-old woman was referred to our department for further investigation of anaemia. Blood test showed macrocytic anaemia. Oesophagogastroduodenoscopy (OGD) revealed proximal-predominant gastric atrophy and flat elevated lesion in the gastric body. Several days after OGD, she complained of gait disturbance and was diagnosed with subacute combined degeneration of the spinal cord. Furthermore, laboratory tests showed positive for both anti-parietal cell and anti-intrinsic factor antibodies, as well as increased serum gastrin level and decreased pepsinogen I level, which confirmed the diagnosis of autoimmune gastritis (AIG). Anaemia and neurological symptoms were improved after vitamin B12 supplementation. Subsequently, the patient underwent gastric endoscopic submucosal dissection; histopathological examination revealed gastric adenoma. AIG can cause gastric neoplasms and vitamin B12 deficiency, with the latter resulting in pernicious anaemia and neurological disorders. These diseases are treatable but potentially life-threatening. This case highlights the importance of early diagnosis of AIG and proper management of its comorbidities.


Assuntos
Adenoma , Doenças Autoimunes , Gastrite , Neoplasias Gástricas , Degeneração Combinada Subaguda , Deficiência de Vitamina B 12 , Adenoma/patologia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Feminino , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/patologia , Humanos , Pessoa de Meia-Idade , Medula Espinal/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico
16.
Front Immunol ; 12: 653786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981305

RESUMO

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/complicações , Mielite Transversa/complicações , SARS-CoV-2/patogenicidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielite Transversa/diagnóstico , Mielite Transversa/patologia , Mielite Transversa/fisiopatologia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Tropismo Viral , Adulto Jovem
17.
Exp Parasitol ; 225: 108112, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33964315

RESUMO

Matrix metalloproteinases (MMPs), are implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Our aim was to investigate whether amelioration of EAE in Dark Agouti (DA) rats, induced by Trichinella spiralis muscle larvae excretory-secretory products (ES L1), could be related to the level and activity of gelatinases, MMP-9 and MMP-2. Serum levels of MMP-9, MMP-2, NGAL/MMP-9, TIMP-1, and cytokines, evaluated by gel-zymography or ELISA, as well as gelatinases and TIMP-1 expression in the spinal cord (SC), were determined in: i) EAE induced, ii) ES L1-treated EAE induced animals. Milder clinical signs in ES L1-treated EAE induced DA rats were accompanied with lower serum levels of MMP-9 and NGAL/MMP-9 complex. However, the correlation between the severity of EAE and the level of serum MMP-9 was found only in the peak of the disease, with MMP-9/TIMP-1 ratio higher in EAE animals without ES L1 treatment. Lower expression of MMP-9 in SC of ES L1-treated, EAE induced rats, correlated with the reduced number of SC infiltrating cells. In SC infiltrates, in the effector and the recovery phase, production of anti-inflammatory cytokines IL-4 and IL-10 was higher in animals treated with ES L1 prior to EAE induction, compared to untreated EAE animals. Reduced expression of MMP-9 in SC tissue, which correlated with the reduced number of infiltrating cells, might be ascribed to regulatory mechanisms, among which is IL-10.


Assuntos
Antígenos de Helmintos/uso terapêutico , Encefalomielite Autoimune Experimental/metabolismo , Proteínas de Helminto/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Trichinella spiralis/metabolismo , Animais , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Inflamação , Interleucina-10/metabolismo , Ratos , Índice de Gravidade de Doença , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo
18.
Neuroscience ; 465: 11-22, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33945797

RESUMO

Amyotrophic lateral sclerosis (ALS) is one of the leading causes of death associated with neurodegenerative diseases worldwide, and the progression of the disease is characteristically accompanied by severe neuroinflammation. Neuroprotective effects of oxymatrine (OMT) were shown to be due to reduced neuroinflammation in the mouse models of Alzheimer's disease and Parkinson's disease. The present study investigated whether OMT has a therapeutic potential in transgenic SOD1-G93A (TgSOD1-G93A) mice. Daily OMT treatment started at the age of 55 days until the end stage of the disease. Body weight and rotarod motor performance were assessed every 3 days starting from 70 days of age. Footprints were recorded to measure the stride length 40 days and 60 days after the initiation of the treatment. Some animals were sacrificed at the age of 115 days, and the lumbar spinal cord was harvested for immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate the neuroinflammatory responses. The results indicated that treatment with OMT delayed body weight loss, improved motor performance, and prolonged the survival of SOD1-G93A mice. Mechanistically, OMT treatment enhanced motor neuronal survival and alleviated the activation of microglia and astrocytes compared with those in the vehicle-treated group. Furthermore, the expression of the proinflammatory mediators was downregulated, and the expression of the anti-inflammatory factors was upregulated in the OMT-treated group compared with those in the vehicle-treated group (P < 0.05). Thus, the treatment with OMT had neuroprotective effects, promoting neuronal survival and extending the lifetime of SOD1-G93A mice by suppressing neuroinflammation.


Assuntos
Alcaloides , Esclerose Amiotrófica Lateral , Alcaloides/farmacologia , Esclerose Amiotrófica Lateral/tratamento farmacológico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Neurônios Motores , Quinolizinas , Medula Espinal , Superóxido Dismutase/genética , Superóxido Dismutase-1/genética
19.
Nat Commun ; 12(1): 2471, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931636

RESUMO

In vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their rich diversity. Specifically, visceral motor neurons, which provide autonomic control, can be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons is also reflected in our analysis with alpha, gamma, and a third subtype, possibly corresponding to the elusive beta motor neurons, clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.


Assuntos
Neurônios Colinérgicos/citologia , Interneurônios/citologia , Neurônios Motores/citologia , Análise de Célula Única/métodos , Núcleo Solitário/metabolismo , Medula Espinal/metabolismo , Transcriptoma/genética , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/fisiologia , Feminino , Hibridização In Situ , Interneurônios/metabolismo , Interneurônios/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , RNA-Seq , Medula Espinal/citologia , Medula Espinal/fisiologia
20.
Acta Cir Bras ; 36(3): e360307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978063

RESUMO

PURPOSE: To probe the mechanism of mild hypothermia combined with rutin in the treatment of spinal cord injury (SCI). METHODS: Thirty rats were randomized into the following groups: control, sham, model, mild hypothermia (MH), and mild hypothermia plus rutin (MH+Rutin). We used modified Allen's method to injure the spinal cord (T10) in rats, and then treated it with MH or/and rutin immediately. BBB scores were performed on all rats. We used HE staining for observing the injured spinal cord tissue; ELISA for assaying TNF-α, IL-1ß, IL-8, Myeloperoxidase (MPO), and Malondialdehyde (MDA) contents; Dihydroethidium (DHE) for measuring the reactive oxygen species (ROS) content; flow cytometry for detecting apoptosis; and both RT-qPCR and Western blot for determining the expression levels of TGF-ß/Smad pathway related proteins (TGF-ß, Smad2, and Smad3). RESULTS: In comparison with model group, the BBB score of MH increased to a certain extent and MH+Rutin group increased more than MH group (p < 0.05). After treatment with MH and MH+Rutin, the inflammatory infiltration diminished. MH and MH+Rutin tellingly dwindled TNF-ß, MDA and ROS contents (p < 0.01), and minified spinal cord cell apoptosis. MH and MH+Rutin could patently diminished TGF-ß1, Smad2, and Smad3 expression (p < 0.01). CONCLUSIONS: MH+Rutin can suppress the activation of TGF-ß/Smad pathway, hence repressing the cellular inflammatory response after SCI.


Assuntos
Hipotermia , Traumatismos da Medula Espinal , Animais , Ratos , Ratos Sprague-Dawley , Rutina/uso terapêutico , Medula Espinal , Traumatismos da Medula Espinal/terapia , Fator de Crescimento Transformador beta
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