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1.
Acta Cir Bras ; 35(3): e202000301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401830

RESUMO

PURPOSE: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. METHODS: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. RESULTS: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. CONCLUSIONS: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.


Assuntos
Anemia Falciforme/tratamento farmacológico , Encéfalo/metabolismo , Hidroxiureia/uso terapêutico , Fígado/metabolismo , Estresse Oxidativo/fisiologia , Medula Espinal/metabolismo , Anemia Falciforme/metabolismo , Anemia Falciforme/fisiopatologia , Animais , Modelos Animais de Doenças , Masculino , NG-Nitroarginina Metil Éster , Ratos , Ratos Wistar
3.
J Biol Regul Homeost Agents ; 34(1): 25-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32264665

RESUMO

Neuropathic pain (NP) after spinal cord injury (SCI) leads to compromised physical and cognitive functions in a majority of patients. Aberrant miRNA expression plays vital roles in the pathogenesis of SCI. This study aims to investigate the effect of miR-331-3p in rats following SCI. Microarray assay was performed in SCI- and sham-operated rats to evaluate the expression of miR-331-3p. Assigned SCI rats were treated with miR-331-3p agomiR alone or miR-331-3p agomiR plus RAP1A-expressing lentivirus or control agomiR. Rat locomotor performance was evaluated by BBB locomotor rating scale. Neuronal tissue damage and apoptosis were detected by histological analyses and Western blot. Inflammation in spinal cord was determined by detection of the expression of inflammatory genes with qRT-PCR, and ELISA. Downstream expression of RAP1A was measured by Western blot. The results showed that SCI induced the downregulation of miR-331-3p in the spinal cord of SCI rats. Overexpression of miR-331-3p improved the locomotor performance, reduced tissue damage, neuronal apoptosis and inflammation in rat SCI model. Rap1a (Ras-related protein Rap-1A) was predicted as a downstream target for miR-331-3p, and upregulation of RAP1A impaired the beneficial effect of miR-331-3p post- SCI, which was shown as worse locomotor activity, more severe tissue damage, as well as promoting apoptosis and inflammation in SCI rats. Furthermore, miR-331-3p reduced the activation of RAP1A downstream genes via inhibiting RAP1A expression. These findings indicate a protective role of miR- 331-3p in the development of SCI via the modulation of RAP1A, and may help to develop novel therapy against SCI-induced complications.


Assuntos
MicroRNAs/genética , Neuralgia/genética , Traumatismos da Medula Espinal/patologia , Proteínas rap1 de Ligação ao GTP/genética , Animais , Ratos , Ratos Sprague-Dawley , Medula Espinal
4.
Int. j. morphol ; 38(2): 259-264, abr. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056432

RESUMO

The family of paired box (Pax) genes encodes the transcription factors that have been emphasized for the particular importance to embryonic development of the CNS, with the evidence obtained from various animal models. Human embryos have rarely been available for the detection of the expression of Pax family members. In this study 32 human embryos of Carnegie (CS) stages 10-20 were investigated to find the differences in the expression of Pax6 and Pax7 proteins in different regions of the neural tube and the caudal spinal cord. The expression of Pax6 and Pax7, as determined by immunohistochemistry, showed a tendency to increase in the later stages of the development both in the spinal cord and the brain. Significantly weaker expression of Pax6 and Pax7 was observed at CS 10 as compared to the later stages. At CS 10-12 weak expression of Pax6 was noticed in both dorsal and ventral parts of the developing spinal cord, while the expression of Pax7 was restricted to the cells in the roof plate and the dorsal part of the spinal cord. At CS 14-20 in the developing spinal cord Pax6 and Pax7 were detected mostly in the neuroepithelial cells of the ventricular layer, while only weak expression characterized the mantle and the marginal layers. At the same stages in the developing brain Pax6 and Pax7 were expressed in the different regions of the forebrain, the midbrain and the hindbrain suggesting for their involvement in the differentiation of neurons in specific parts of the developing brain.


La familia de genes Pax del inglés (Paired box) codifica los factores de transcripción debido a la particular importancia en el desarrollo embrionario del SNC, con la evidencia obtenida de varios modelos animales. Rara vez han estado disponibles embriones humanos para la detección de la expresión de genes de la familia Pax. En este estudio, se investigaron 32 embriones humanos de Carnegie (CS) etapas 10-20 para encontrar las diferencias en la expresión de las proteínas Pax6 y Pax7 en diferentes regiones del tubo neural y la médula espinal caudal. La expresión de Pax6 y Pax7, según la inmunohistoquímica, se observó una tendencia a aumentar en las etapas posteriores del desarrollo, tanto en la médula espinal como en el cerebro. Se observó una expresión significativamente más débil de Pax6 y Pax7 en CS 10 en comparación con las etapas posteriores. En CS 10-12 se notó una expresión débil de Pax6 en las partes dorsal y ventral de la médula espinal en desarrollo, mientras que la expresión de Pax7 se limitó a células en la placa del techo y dorsal de la médula espinal. En CS 14-20 en la médula espinal en desarrollo, Pax6 y Pax7 se observó principalmente en las células neuroepiteliales de la capa ventricular, mientras que expresión débil se caracterizó en las capas marginales. En las mismas etapas en el cerebro en desarrollo, Pax6 y Pax7 se expresaron en las diferentes áreas del prosencéfalo, el mesencéfalo y el mesencéfalo, lo que sugiere su participación en la diferenciación de las neuronas en partes específicas del cerebro en desarrollo.


Assuntos
Humanos , Medula Espinal/metabolismo , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Embrionário , Fator de Transcrição PAX7/metabolismo , Fator de Transcrição PAX6/metabolismo , Medula Espinal/embriologia , Encéfalo/embriologia , Imuno-Histoquímica
5.
Zhongguo Gu Shang ; 33(2): 131-5, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32133811

RESUMO

OBJECTIVE: To analyze the effectiveness and safety of one stage three column osteotomy in treatment of scoliosis with split spinal cord malformation. METHODS: The clinical data of 41 patients with scoliosis and split spinal cord malformation underwent one-stage three-column osteotomy from January 2015 to December 2017 were retrospectively analyzed. There were 17 males and 24 females with average age of (25.14±4.51) years old and the average weight of (65.14±9.11) kg. According to the classification of longitudinal spina bifida, 15 cases of Pang typeⅠwere group A and 26 cases of Pang typeⅡwere group B. The general situations of two groups were recorded ; preoperative and postoperative Cobb angle were observed and the correction rate of Cobb angle of coronal plane was calculated ; the coronal and sagittal torso offset distances were compared between two groups and the trunk balance was evaluated ; the complication of two groups was recorded. RESULTS: All 41 patients were followed up for more than 12 months. The operation time, intraoperative blood loss, and perioperative blood transfusion volume in group A were (610.14±115.02) min, (4 001.12±1 014.33) ml, (3 951.14±1 021.55) ml, respectively, and group B were (520.12±101.14) min, (2 701.57±1 021.45) ml, (2 565.77±880.47) ml, the difference between the two groups was statistically significant (P<0.05). The postoperative hospital stays in the group A and B were (9.45±4.21) days and (9.14±3.01) days, respectively, and there was no significant difference (P>0.05). There was no significant difference in postoperative coronary Cobb angle and correction rate between two groups (P>0.05). Immediately after surgery and 12 months after surgery, there was no significant difference in the trunk displacement distance of coronal view and sagittal view between two groups (P>0.05). Six patients in group A had complications, which was higher than that in group B of 1 case (χ2=4.885, P< 0.05). CONCLUSION: One-stage three-column osteotomy in treatment of scoliosis with split spinal cord malformation has high correction rate and good balance of the trunk. However, for patients with typeⅠsplit spinal cord malformation, they will face longer operation time, more intraoperative bleeding volume, large amount of perioperative blood transfusion and higher risk of complications, and the safety is not as good as that of typeⅡpatients. Therefore, in the actual treatment of scoliosis, especially for those with typeⅠsplit spinal cord malformation, a more reasonable surgical plan should be developed in combination with the actual situations of the patients, so as to improve the safety of the operation.


Assuntos
Escoliose , Fusão Vertebral , Adulto , Feminino , Humanos , Masculino , Osteotomia , Estudos Retrospectivos , Escoliose/cirurgia , Medula Espinal , Resultado do Tratamento , Adulto Jovem
6.
PLoS One ; 15(3): e0226584, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191733

RESUMO

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-alpha, IL-1beta, IFN-gamma and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.


Assuntos
Aracnoidite/imunologia , Gliose/imunologia , Traumatismos da Medula Espinal/complicações , Medula Espinal/patologia , Animais , Anti-Inflamatórios , Aracnoidite/diagnóstico , Aracnoidite/patologia , Astrócitos/imunologia , Astrócitos/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Gliose/diagnóstico , Gliose/patologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Masculino , Bainha de Mielina/imunologia , Bainha de Mielina/patologia , Ratos , Índice de Gravidade de Doença , Medula Espinal/citologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/imunologia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/patologia , Fatores de Tempo
7.
Life Sci ; 250: 117557, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32184124

RESUMO

Diabetic neuropathy (DN) is a common complication of diabetes mellitus (DM). Pathophysiology of DN includes inflammation and changes in expression and function of voltage-gated sodium channels (Nav) in peripheral nerves; and central reduction of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) expression. AIM: This study explored the effect of ranolazine (RN) versus pioglitazone (PIO) in DN induced in rats. The role of sciatic interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, Nav1.7, and spinal PPAR-γ expressions were determined. MATERIALS AND METHODS: For induction of Type-2 DM, 40 high fat diet-fed rats were challenged by a single dose of intraperitoneal streptozotocin (30 mg/kg). One week later, oral PIO (10 mg/kg; once daily) or RN (20, 50 and 100 mg/kg; twice daily) were administered for six weeks. Weekly body weight and fasting blood sugar (FBS) were measured. Rats were tested for thermal hyperalgesia and mechanical allodynia. At the end of the experiment, sciatic nerves homogenates were examined for TNF-α and IL-1B levels, and Nav1.7 channel expression. Segments of spinal cords were investigated for the PPAR-γ gene expression. Evaluation of histopathology of sciatic nerves and spinal cords were done. KEY FINDINGS: In diabetic rats, PIO and RN individually improved evoked-pain behaviors, reduced sciatic TNF-α and 1L-1B levels; downregulated expressional levels of Nav1.7 channels; and increased the spinal PPAR-γ gene expression. RN in the dose of 100 mg/kg/day showed the most advantageous effects. SIGNIFICANCE: RN has neuroprotective effects in Type-2 diabetes-induced DN. Further studies of combined RN-PIO treatment are recommended, especially in diabetic patients with cardiovascular co-morbidity.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Fármacos Neuroprotetores/uso terapêutico , PPAR gama/metabolismo , Pioglitazona/uso terapêutico , Ranolazina/uso terapêutico , Animais , Comportamento Animal , Comorbidade , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica , Hiperalgesia , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Coluna/Columna ; 19(1): 8-12, Jan.-Mar. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1089646

RESUMO

ABSTRACT Objective The spinal cord extends from the foramen magnum to the sacrum in the human fetus at the beginning of the 2nd quarter. However, the medullary cone is located at or above the level of the second lumbar vertebra at birth. The objective is to determine the difference between the rates of longitudinal growth of the spinal cord and the spine in human fetuses from the 13th to the 22nd week of gestation (WoG) using magnetic resonance imaging (MRI). Methods Descriptive observational cross-sectional study of 24 stillbirths (13 ♂, 11 ♀), between the 13th and 22nd WoG, using spinal MRI. We recorded spine and spinal cord lengths in millimeters from the foramen magnum to the coccyx for the former and to the medullary cone for the latter. We identified the position of the medullary cone according to vertebral level and its correlation with the gestational age and the literature. Results The spinal cord increased in length from 50 to 93 mm, the spine from 57 to 137 mm, and the medullary cone rose from S1 to L2. The rate of growth was 1.2 mm/day for the spine and 0.6 mm/day for the spinal cord. Conclusions Discordance in the rate of normal longitudinal growth of the spine and spinal cord caused the medullary cone to rise from S1 level to L2 in the second trimester of pregnancy. These results allow an understanding of normal development and certain congenital malformations. Level of evidence IV; Case series.


RESUMO Objetivo A medula espinhal (ME) estende-se desde o forame magno até o sacro no feto humano no início do 2º trimestre. No entanto, ao nascimento, o cone medular localiza-se no nível da segunda vértebra lombar ou acima. O objetivo é determinar as diferenças na taxa de crescimento longitudinal da ME e da coluna vertebral (CV) em fetos humanos da 13a à 22a semana de gestação (SG) por meio de ressonância magnética (RM). Métodos Estudo observacional transversal descritivo em 24 natimortos (13 ♂, 11 ♀), com idades entre 13ª e 22ª SG, por RM da CV. O comprimento da CV e da ME foi registrado em milímetros, desde o forame magno até o cóccix na CV e até o cone na ME. Identificou-se a posição do cone de acordo com o nível vertebral, sua correlação com a idade gestacional e com literatura. Resultados O comprimento da ME aumentou de 50 para 93 mm, a CV de 57 para 137 mm e o cone medular subiu de S1 para L2. O ritmo de crescimento foi de 1,2 mm/dia para a CV e de 0,6 mm/dia para a ME. Conclusões A discordância no ritmo do crescimento longitudinal normal da CV e da ME fez com que o cone medular subisse do nível de S1 até L2 no segundo trimestre de gravidez. Os resultados permitem compreender o desenvolvimento normal e certas malformações congênitas. Nível de evidência IV; Série de casos.


RESUMEN Objetivo La médula espinal (ME) se extiende desde el foramen magnum hasta el sacro en el feto humano al inicio del 2º trimestre. Sin embargo, el cono medular se ubica a nivel de la segunda vertebral lumbar o por encima en el momento del nacimiento. El objetivo es determinar las diferencias en el ritmo de crecimiento longitudinal de la ME y columna vertebral (CV) en fetos humanos desde la 13ª hasta la 22ª semana de gestación (SG) mediante resonancia magnética (RM). Métodos Estudio descriptivo observacional transversal en 24 mortinatos (13 ♂, 11 ♀), con edades entre la 13ª y 22ª SG, mediante RM de CV. Se registró la longitud de CV y ME, en milímetros, desde el foramen mágnum al coxis en la primera y hasta el cono en la segunda. Se identificó la posición del cono según el nivel vertebral y su correlación con edad gestacional y literatura. Resultados La ME incrementó su longitud de 50 a 93 mm, la CV de 57 a 137 mm y el cono medular ascendió desde S1 hasta L2. El ritmo de crecimiento fue de 1.2 mm/día para la CV y de 0.6 mm/día para la ME. Conclusiones La discordancia en el ritmo de crecimiento longitudinal normal de la CV y ME determinó que el cono medular ascienda desde el nivel S1 hasta L2 en el segundo trimestre de gestación. Los resultados permiten comprender el desarrollo normal y ciertas malformaciones congénitas. Nivel de evidencia IV, serie de casos.


Assuntos
Humanos , Medula Espinal , Coluna Vertebral , Desenvolvimento Fetal
10.
Zhen Ci Yan Jiu ; 45(1): 40-5, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144907

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Jiaji" (EX-B2) at different time points on the expression of OX-42 (a monoclonal antibody with specific expression of complement receptor-3 in spinal microglial cells) and purinergic receptor P2X4 (P2X4) in rats with chronic constriction injury (CCI) of the sciatic nerve, as well as the possible after-effect mechanism of EA analgesia in neuropathic pain. METHODS: Sprague-Dawley rats were randomly divided into blank group, model group, immediately after EA group, 0.5-hour after EA group, 1-hour after EA group, 2-hour after EA group, 4-hour after EA group, 12-hour after EA group, and 24-hour after EA group, with 6 rats in each group. The rats in the model group and the EA groups were used to establish a model of CCI-induced neuropathic pain, and those in the immediately after EA group and the 0.5, 1, 2, 4, 12 and 24 hours after EA groups were treated with EA at bilateral L3 and L5 "Jiaji" points for 20 min after 7 d of modeling. Samples were collected immediately and at 0.5, 1, 2, 4, 12, and 24 hours after EA, and for the rats in the blank group and the model group, samples were collected after fixation the rats for 20 min. Heat pain threshold was observed before and after intervention, and immunohistochemistry was used to measure the protein expression of OX-42 and P2X4 in the spinal cord lumbar enlargement. RESULTS: After 7 days of modeling (before intervention), compared with the blank group, the heat pain threshold had a significant reduction in the model group and the EA groups (P<0.01). Compared with the model group after intervention, the immediately after EA group and the 0.5, 1 and 2 hours after EA groups had a significant increase in heat pain threshold (P<0.05). Compared with the model group, immediately after EA, the 0.5, 1 and 2 hours after EA groups had a significant reduction in the protein expression of OX-42 (P<0.01), and immediately after EA, the 0.5 and 1 hour after EA groups had a significant reduction in the protein expression of P2X4 (P<0.01). CONCLUSION: EA at "Jiaji" points can significantly increase heat pain threshold and down-regulate the protein expression of OX-42 and P2X4 in the spinal cord of CCI rats. The analgesic effect can last for 2 h.


Assuntos
Eletroacupuntura , Analgésicos , Animais , Constrição , Regulação para Baixo , Ratos , Ratos Sprague-Dawley , Medula Espinal
11.
Zhen Ci Yan Jiu ; 45(2): 157-63, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144928

RESUMO

OBJECTIVE: To investigate the specific regularity of body surface resistance at different acupoints of the meridians associated with the uterus in reflecting menstrual cycle by observing the change in body surface resistance at source points, cleft points, confluent points, and non-specific points of three yin meridians of the foot in different menstrual cycles in normal female college students, to lay a foundation for the in-depth research on the mechanism of acupoints reflecting the function of zang-fu, and to provide a reference for the clinical and scientific research on the biophysical characteristics of menstrual cycle-related acupoints in normal female. METHODS: A total of 90 normal female college students were recruited. The source points, cleftpoints, confluent points, and non-specific points of three yin meridians of the foot which were located in the adjacent spinal segments of the uterus were selected, and body surface resistance was monitored for 30 consecutive minutes at the same time-points of menstrual phase, follicular phase, ovulation phase, and luteal phase to observe the change in the resistance of each acupoint during the menstrual cycle. RESULTS: There was no significant change in the resistance value of unilateral acupoints during the menstrual cycle (P>0.05). In the same period, there was no significant difference in resistance value between unilateral three source points, three cleftpoints, different acupoints of the spleen meridian, and different acupoints of lumbar 4 dermatomere (P>0.05). As for the comparison of resistance of the same acupoint at the left and right sides, Taichong (LR3) at the left side had a higher resistance value than that at the right side in the menstrual phase (P<0.05); Taibai (SP3) at the left side had a higher resistance value than that at the right side in the ovulation phase (P<0.05); Zhongdu (LR6) at the left side had a higher resistance value than that at the right side in the follicular phase, the ovulation phase, and the luteal phase (P<0.05); Taixi (KI3), Diji (SP8), and Sanyinjiao (SP6) at the left side had a higher resistance value than those at the right side in the menstrual phase, the follicular phase, the ovulation phase, and the luteal phase (P<0.05); Shuiquan (KI5) at the left side had a lower resistance value than that at the right side in these four phases (P<0.05). CONCLUSION: The change trend of the resistance of the acupoints at the left and right sides associated with the three yin meridians of the foot can specifically reflect the change in qi and blood in the uterus during the menstrual cycle. The change trend of the source and cleft points of the liver meridian in the menstrual phase is different from that in the other phases, and the change trend of SP3, a source point of the spleen meridian, in the ovulation phase is different from that in the other phases, which suggests the specificity of meridian points in reflecting function. The mechanism by which meridian points reflect the function of zang-fu is associated with the meridian points and the spinal cord segments of zang-fu, and meanwhile, it has a specific relationship with the meridians to which meridian points belong and the attributes of acupoints.


Assuntos
Pontos de Acupuntura , Meridianos , Feminino , Humanos , Medula Espinal , Útero
12.
Ann R Coll Surg Engl ; 102(5): e94-e96, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32003581

RESUMO

A woman in her late sixties was referred to the orthopaedic clinic with progressive lower limb weakness and gait disturbance. She was known to have breast cancer with pre-existing infiltrative disease in the left brachial plexus. Magnetic resonance imaging of the spine revealed an intramedullary spinal cord metastasis in the lower cervical cord at C6-C7. She underwent surgical excision but died within six weeks of surgery. This rare case of an intramedullary spinal cord metastasis highlights the extremely poor prognosis in this condition as well as the possibility of perineural invasion into the spinal cord from the brachial plexus lesion. A detailed discussion of the literature on intramedullary spinal cord metastases is also presented.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Medula Espinal/secundário , Medula Espinal/patologia , Evolução Fatal , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Prognóstico , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia
13.
Nucleic Acids Res ; 48(6): 2853-2865, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32103257

RESUMO

Spinal muscular atrophy (SMA) is a motor neuron disease. Nusinersen, a splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA. Based on prior preclinical studies, both 2'-O-methoxyethyl (MOE) with a phosphorothioate backbone and morpholino with a phosphorodiamidate backbone-with the same or extended target sequence as nusinersen-displayed efficient rescue of SMA mouse models. Here, we compared the therapeutic efficacy of these two modification chemistries in rescue of a severe mouse model using ASO10-29-a 2-nt longer version of nusinersen-via subcutaneous injection. Although both chemistries efficiently corrected SMN2 splicing in various tissues, restored motor function and improved the integrity of neuromuscular junctions, MOE-modified ASO10-29 (MOE10-29) was more efficacious than morpholino-modified ASO10-29 (PMO10-29) at the same molar dose, as seen by longer survival, greater body-weight gain and better preservation of motor neurons. Time-course analysis revealed that MOE10-29 had more persistent effects than PMO10-29. On the other hand, PMO10-29 appears to more readily cross an immature blood-brain barrier following systemic administration, showing more robust initial effects on SMN2 exon 7 inclusion, but less persistence in the central nervous system. We conclude that both modifications can be effective as splice-switching ASOs in the context of SMA and potentially other diseases, and discuss the advantages and disadvantages of each.


Assuntos
Amidas/química , Morfolinos/uso terapêutico , Atrofia Muscular Espinal/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Ácidos Fosfóricos/química , Animais , Modelos Animais de Doenças , Éxons/genética , Humanos , Camundongos Transgênicos , Morfolinos/farmacologia , Atividade Motora/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Músculos/patologia , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/fisiopatologia , Junção Neuromuscular/patologia , Junção Neuromuscular/fisiopatologia , Oligonucleotídeos Antissenso/farmacologia , Fenótipo , Processamento de RNA/efeitos dos fármacos , Processamento de RNA/genética , Medula Espinal/patologia , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Resultado do Tratamento
14.
Int J Nanomedicine ; 15: 17-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021162

RESUMO

Background: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical application for systemic administration. Purpose: This study aims to develop a novel formulation of nanosome-encapsulated honokiol (NHNK) for intravenous therapy against mouse experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis. Methods: Nanosomes and NHNK were prepared by using an ultra-high pressure homogenization (UHPH) method. Mice were treated with NHNK or empty nanosomes during the peak phase of EAE symptoms. Symptoms of EAE were monitored and samples of the spinal cord were obtained for histopathological examinations. Results: The stock of NHNK containing honokiol in the nanosome formulation, which showed the structure of single phospholipid bilayer membranes, was well formulated with the particle size of 48.0 ± 0.1 nm and the encapsulation efficiency 58.1 ± 4.2%. Intravenous administration of NHNK ameliorated the severity of EAE accompanied by a significant reduction of demyelination and inflammation in the spinal cord. Furthermore, NHNK decreased the number of IL-6+, Iba-1+TNF +, Iba-1+IL-12 p40+, and CD3+IFN-γ+ cells infiltrating the spinal cord. Conclusion: The UHPH method simplified the preparation of NHNK with uniformly distributed nanosize and high encapsulation efficiency. Intravenous administration of NHNK ameliorated the severity of EAE by suppressing the infiltration of activated microglia and Th1 cells into the spinal cord. Collectively, these results suggest that the formulation of NHNK is a prospective therapeutic approach for inflammatory CNS diseases, such as multiple sclerosis.


Assuntos
Compostos de Bifenilo/administração & dosagem , Encefalomielite Autoimune Experimental/tratamento farmacológico , Lignanas/administração & dosagem , Nanoestruturas/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Encefalomielite Autoimune Experimental/etiologia , Feminino , Injeções Intravenosas , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/etiologia , Mielite/tratamento farmacológico , Mielite/etiologia , Nanoestruturas/química , Fármacos Neuroprotetores/farmacologia , Medula Espinal/patologia , Células Th1/efeitos dos fármacos , Células Th1/patologia
15.
Arq Neuropsiquiatr ; 78(1): 21-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32074185

RESUMO

OBJECTIVE: The phytohormone abscisic acid (ABA) as a signaling molecule exists in various types of organisms from early multicellular to animal cells and tissues. It has been demonstrated that ABA has an antinociceptive effect in rodents. The present study was designed to assess the possible role of PKA and phosphorylated ERK (p-ERK) on the antinociceptive effects of intrathecal (i.t.) ABA in male Wistar rats. METHODS: The animals were cannulated intrathecally and divided into different experimental groups (n=6‒7): Control (no surgery), vehicle (received ABA vehicle), ABA-treated groups (received ABA in doses of 10 or 20 µg/rat), ABA plus H.89 (PKA inhibitor)-treated group which received the inhibitor 15 min prior to the ABA injection. Tail-flick and hot-plate tests were used as acute nociceptive stimulators to assess ABA analgesic effects. p-ERK was evaluated in the dorsal portion of the spinal cord using immunoblotting. RESULTS: Data showed that a microinjection of ABA (10 and 20 µg/rat, i.t.) significantly increased the nociceptive threshold in tail flick and hot plate tests. The application of PKA inhibitor (H.89, 100 nM/rat) significantly inhibited ABA-induced analgesic effects. Expression of p-ERK was significantly decreased in ABA-injected animals, which were not observed in the ABA+H.89-treated group. CONCLUSIONS: Overall, i.t. administration of ABA (10 µg/rat) induced analgesia and p-ERK down-expression likely by involving the PKA-dependent mechanism.


Assuntos
Ácido Abscísico/farmacologia , Analgésicos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Medula Espinal/metabolismo , Animais , Western Blotting , Proteínas Quinases Dependentes de AMP Cíclico/análise , MAP Quinases Reguladas por Sinal Extracelular/análise , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Masculino , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Medula Espinal/efeitos dos fármacos , Fatores de Tempo
16.
Nat Commun ; 11(1): 1004, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081878

RESUMO

Cytoplasmic aggregation of TDP-43 characterizes degenerating neurons in most cases of amyotrophic lateral sclerosis (ALS). Here, we develop an optogenetic TDP-43 variant (opTDP-43), whose multimerization status can be modulated in vivo through external light illumination. Using the translucent zebrafish neuromuscular system, we demonstrate that short-term light stimulation reversibly induces cytoplasmic opTDP-43 mislocalization, but not aggregation, in the spinal motor neuron, leading to an axon outgrowth defect associated with myofiber denervation. In contrast, opTDP-43 forms pathological aggregates in the cytoplasm after longer-term illumination and seeds non-optogenetic TDP-43 aggregation. Furthermore, we find that an ALS-linked mutation in the intrinsically disordered region (IDR) exacerbates the light-dependent opTDP-43 toxicity on locomotor behavior. Together, our results propose that IDR-mediated TDP-43 oligomerization triggers both acute and long-term pathologies of motor neurons, which may be relevant to the pathogenesis and progression of ALS.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Esclerose Amiotrófica Lateral/genética , Animais , Animais Geneticamente Modificados , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Modelos Moleculares , Mutação , Optogenética , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Multimerização Proteica , Estabilidade Proteica , Regulação para Cima , Peixe-Zebra
17.
Ideggyogy Sz ; 73(1-2): 7-14, 2020 Jan 30.
Artigo em Húngaro | MEDLINE | ID: mdl-32057199

RESUMO

Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Encéfalo/diagnóstico por imagem , Progressão da Doença , Humanos , Imagem por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/terapia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/terapia , Medula Espinal
19.
Medicine (Baltimore) ; 99(6): e19031, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028416

RESUMO

The study was designed to verify if mini-fluid challenge test is more reliable than dynamic fluid variables in predicting stroke volume (SV) and arterial pressure fluid responsiveness during spine surgery in prone position with low-tidal-volume ventilation.Fifty patients undergoing spine surgery in prone position were included. Fluid challenge with 500 mL of colloid over 15 minutes was given. Changes in SV and systolic blood pressure (SBP) after initial 100 mL were compared with SV, pulse pressure variation (PPV), SV variation (SVV), plethysmographic variability index (PVI), and dynamic arterial elastance (Eadyn) in predicting SV or arterial pressure fluid responsiveness (15% increase or greater).An increase in SV of 5% or more after 100 mL predicted SV fluid responsiveness with area under the receiver operating curve (AUROC) of 0.90 (95% confidence interval [CI], 0.82 to 0.99), which was significantly higher than that of PPV (0.71 [95% CI, 0.57 to 0.86]; P = .01), and SVV (0.72 [95% CI, 0.57 to 0.87]; P = .03). A more than 4% increase in SBP after 100 mL predicted arterial pressure fluid responsiveness with AUROC of 0.86 (95% CI, 0.71-1.00), which was significantly higher than that of Eadyn (0.52 [95% CI, 0.33 to 0.71]; P = .01).Changes in SV and SBP after 100 mL of colloid predicted SV and arterial pressure fluid responsiveness, respectively, during spine surgery in prone position with low-tidal-volume ventilation.


Assuntos
Pressão Sanguínea , Monitorização Intraoperatória/métodos , Posicionamento do Paciente , Medula Espinal/cirurgia , Volume Sistólico , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia/métodos , Decúbito Ventral , Estudos Prospectivos , Adulto Jovem
20.
Medicine (Baltimore) ; 99(3): e18794, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011480

RESUMO

RATIONALE: Spinal involvement in adult Langerhans cell histiocytosis (LCH) is rare, and epidural involvement is unusual. LCH is mostly indistinguishable from other spinal lesions such as infection, lymphoma, and metastasis. So, it could be easily misdiagnosed without suspicion. PATIENT CONCERNS: We report a case of a 33-year-old man who complained of gait disturbance with weakness in both legs and severe back pain. DIAGNOSES: A continuous enhancing epidural lesion with cord compression from the T7 to L1 level was detected in magnetic resonance imaging. Laboratory analysis indicated the possibility of spinal infectious disease. We assumed that the lesion could be tuberculous spondylitis. INTERVENTIONS AND OUTCOMES: The patient underwent posterior laminectomy with marginal excision of the epidural mass to relieve cord compression. Pathological examination confirmed the diagnosis of LCH. The 12-month follow-up evaluation revealed that the patient was neurologically intact and had no gait disturbance. LESSONS: This case report presents a patient with epidural LCH of the thoracic spinal cord, which can mimic spinal infections such as tuberculous spondylitis with abscess formation. Therefore, LCH could be considered as a possible diagnosis when a patient presents with features of infectious spondylitis with vertebral involvement.


Assuntos
Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/etiologia , Adulto , Diagnóstico Diferencial , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/cirurgia , Humanos , Masculino , Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Vértebras Torácicas
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