RESUMO
Objectives: Honey contains phenolic acids and flavonoids, which are significant in developing drugs against neuroinflammation. The study was designed to evaluate the ameliorative potential of honey in lipopolysaccharides-induced neuroinflammation.Methods: Thirty male Wistar rats were divided into six groups, namely: the control group (10â mL/kg vehicle), the LPS only group (250â µg/kg), the honey (0.26, 0.31 and 0.36â g/kg) and the ibuprofen (100â mg/kg). LPS (250â µg/kg i.p) was administered for 7days followed by the treatment with honey and Ibuprofen for another 7days. Animals were assessed for memory impairment and anxiety levels using a Novel object recognition test (NORT), elevated plus maze (EPM), and open field test (OFT). Brain levels of pro-inflammatory cytokine level, acetylcholinesterase activity, and oxidative stress were determined. The neuronal alteration was assessed histologically using cresyl fast violet staining of the hippocampus, prefrontal cortex, and striatum.Results: Honey (0.31 and 0.36â g/kg) significantly ameliorated LPS-induced memory impairment on NORT and increased time spent in the open arm and increased the locomotor activity in the OFT. Honey significantly (p < 0.05) reduced LPS-induced elevation of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). It significantly reduced malondialdehyde and nitrite levels in mice brains and reversed depletion of reduced glutathione levels. Honey attenuated LPS-induced elevation of acetylcholinesterase activity in rat brains. Cresyl violet staining showed the restoration of neuronal organization and Nissl body distribution in the hippocampus, prefrontal cortex and striatum compared to the LPS only group.Discussion: Honey effectively ameliorated LPS-induced poor cognitive performance, anxiety, motor coordination responses to neuroinflammation, and oxidative stress.
Assuntos
Ansiedade , Disfunção Cognitiva , Mel , Lipopolissacarídeos , Transtornos da Memória , Transtornos Motores , Doenças Neuroinflamatórias , Lipopolissacarídeos/farmacologia , Ratos , Ratos Wistar , Masculino , Animais , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/prevenção & controle , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Transtornos Motores/induzido quimicamente , Transtornos Motores/prevenção & controle , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Ibuprofeno/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controleRESUMO
OBJECTIVES: Locomotion training (LT) consisting of single-leg standing and squatting was developed to help prevent locomotive syndrome (LS), and is typically used in older people. The objective of this study was to examine the effects of LT on young and middle-aged people. METHODS: This study was performed at two companies. Workers in company A engaged in LT five times/week for 1 year, whereas workers in company B did not. Baseline and follow-up checkups consisted of questionnaires and physical performance tests, including three kinds of locomotion tests. RESULTS: In total, 88 and 101 workers in companies A and B, respectively, met the inclusion criteria. LS stage, stand-up test results, and scores on a geriatric locomotive function scale significantly improved among workers in company A, but only stand-up test results significantly improved among workers in company B. Quadriceps power increased in company A, but did not change in company B. Especially, workers with LS in company A had more significant changes than those without LS and those in company B. CONCLUSIONS: The results of this longitudinal study suggest that LT is useful even for young and middle-aged workers. LT was especially more effective for workers than those without LS.
Assuntos
Locomoção , Saúde Ocupacional , Condicionamento Físico Humano , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Transtornos Motores/prevenção & controle , SíndromeRESUMO
Mutations in KCNC3, the gene that encodes the Kv3.3 voltage dependent potassium channel, cause Spinocerebellar Ataxia type 13 (SCA13), a disease associated with disrupted motor behaviors, progressive cerebellar degeneration, and abnormal auditory processing. The Kv3.3 channel directly binds Hax-1, a cell survival protein. A disease-causing mutation, Kv3.3-G592R, causes overstimulation of Tank Binding Kinase 1 (Tbk1) in the cerebellum, resulting in the degradation of Hax-1 by promoting its trafficking into multivesicular bodies and then to lysosomes. We have now tested the effects of antisense oligonucleotides (ASOs) directed against the Kv3.3 channel on both wild type mice and those bearing the Kv3.3-G592R-encoding mutation. Intracerebroventricular infusion of the Kcnc3-specific ASO suppressed both mRNA and protein levels of the Kv3.3 channel. In wild-type animals, this produced no change in levels of activated Tbk1, Hax-1 or Cd63, a tetraspanin marker for late endosomes/multivesicular bodies. In contrast, in mice homozygous for the Kv3.3-G592R-encoding mutation, the same ASO reduced Tbk1 activation and levels of Cd63, while restoring the expression of Hax-1 in the cerebellum. The motor behavior of the mice was tested using a rotarod assay. Surprisingly, the active ASO had no effects on the motor behavior of wild type mice but restored the behavior of the mutant mice to those of age-matched wild type animals. Our findings indicate that, in mature intact animals, suppression of Kv3.3 expression can reverse the deleterious effects of a SCA13 mutation while having little effect on wild type animals. Thus, targeting Kv3.3 expression may prove a viable therapeutic approach for SCA13.
Assuntos
Transtornos Motores/prevenção & controle , Mutação , Oligonucleotídeos Antissenso/administração & dosagem , Proteínas Serina-Treonina Quinases/metabolismo , Canais de Potássio Shaw/antagonistas & inibidores , Ataxias Espinocerebelares/complicações , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transtornos Motores/etiologia , Transtornos Motores/metabolismo , Transtornos Motores/patologia , Proteínas Serina-Treonina Quinases/genética , Canais de Potássio Shaw/genética , Canais de Potássio Shaw/metabolismoRESUMO
BACKGROUND: In Parkinson's disease (PD), sustained aerobic exercise is a promising therapy in delaying motor disability. Brisk walking is a moderate intensity aerobic training, which could be translated to community practice at low cost, but its effects on motor symptoms remains unclear. OBJECTIVE: To determine the effectiveness of a six-month brisk walking and balance program in alleviating motor symptoms, and promoting functional, gait, and balance performance in people with PD. METHODS: Seventy individuals with mild to moderate PD were randomly assigned to a brisk walking (BW) group or an active control (CON) group. BW group received ten 90-minute supervised brisk walking and balance exercise for six months (weeks 1-6: once/week, weeks 7-26: once/month). CON group received upper limb training. Both groups performed 2-3 self-practice sessions weekly. Primary outcome was Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score. Secondary outcomes were fast gait speed (FGS), timed-up-and-go (TUG) time, six-minute walk distance (6MWD), and Mini-Balance Evaluation Systems Test (Mini-BEST) score. RESULTS: Sixty-four participants (33 BW/31 CON) completed training. BW group showed greater significant decreases from baseline than CON group in MDS-UPDRS motor score after six weeks (-5.5 vs -1.6, pâ<â0.001) and 6 months (-6.0 vs -1.4, pâ<â0.001) of training. BW group also showed greater significant improvement from the baseline than CON group for TUG time, FGS, 6MWD, and mini-BEST score (all pâ<â0.05). CONCLUSION: The six-month brisk walking and balance program alleviates motor symptoms, promotes functional and gait performance, walking capacity, and dynamic balance in people with mild to moderate PD.
Assuntos
Terapia por Exercício , Transtornos Motores , Doença de Parkinson , Serviços de Saúde Comunitária , Humanos , Transtornos Motores/prevenção & controle , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Equilíbrio Postural/fisiologia , Resultado do Tratamento , Caminhada/fisiologiaAssuntos
Academias de Ginástica , Fragilidade/prevenção & controle , Promoção da Saúde/métodos , Vida Independente , Atividade Motora , Transtornos Motores/prevenção & controle , Condicionamento Físico Humano/métodos , Condicionamento Físico Humano/fisiologia , Inquéritos e Questionários , Fatores Etários , Feminino , Humanos , MasculinoRESUMO
Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although several studies have demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), its mechanisms in cerebellar ataxia remain largely unknown. Here, we investigated the neuroprotective effects of H.E. treatment in an animal model of 3-acetylpyridine (3-AP)-induced cerebellar ataxia. Animals administered 3-AP injection exhibited remarkable impairments in motor coordination and balance. There were no significant effects of 25 mg/kg H.E. on the 3-AP treatment group compared to the 3-AP saline group. Interestingly, there was also no significant difference in the 3-AP treatment group compared to the non-3-AP control, indicating a potential rescue of motor deficits. Our results revealed that 25 mg/kg H.E. normalised the neuroplasticity-related gene expression to the level of non-3-AP control. These findings were further supported by increased protein expressions of pERK1/2-pCREB-PSD95 as well as neuroprotective effects on cerebellar Purkinje cells in the 3-AP treatment group compared to the 3-AP saline group. In conclusion, our findings suggest that H.E. potentially rescued behavioural motor deficits through the neuroprotective mechanisms of ERK-CREB-PSD95 in an animal model of 3-AP-induced cerebellar ataxia.
Assuntos
Comportamento Animal/efeitos dos fármacos , Ataxia Cerebelar/tratamento farmacológico , Hericium/crescimento & desenvolvimento , Transtornos Motores/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Piridinas/toxicidade , Animais , Ataxia Cerebelar/induzido quimicamente , Ataxia Cerebelar/psicologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large/genética , Proteína 4 Homóloga a Disks-Large/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hericium/química , Masculino , Transtornos Motores/genética , Transtornos Motores/metabolismo , Transtornos Motores/patologia , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/patologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: The treatment safety and efficiency as well as the life quality of patients are still main concerns in gamma knife radiosurgery. In this study, the feasibility of applying diffusion tensor imaging (DTI) in gamma knife radiosurgery for the treatment of brain tumor in motor function areas was investigated, which aims to provide protection on the pyramidal tract and preserve the motor function in patients. PATIENTS AND METHODS: Total 74 patients with solid brain tumor were enrolled and divided into DTI group and control group. The tumor control rate was assessed at 3 months after surgery. The muscle strength of affected limb, KPS scores, ZEW scores and complications were evaluated at 3 and 6 months after gamma knife radiosurgery. RESULTS: Our results indicated that the tumor control rate, complication rate, the muscle strength of affected limb and KPS scores were not significantly different between the two groups at 3 months after surgery. At 6 months after gamma knife radiosurgery, the complication rate (0% vs 50 %, P = 0.044), KPS scores (64.9 % vs 37.8 %, P = 0.036) and ZEW scores (78.4 % vs 54.1 %, P = 0.044) of DTI group were better than the control group. Furthermore, the stability of muscle strength in patients with limb dysfunction was significantly improved in DTI group (86.4 % vs 50 %, P = 0.028). CONCLUSION: In summary, the application of DTI in gamma knife radiosurgery for the treatment of brain tumors in motor function areas can precisely define the tumor edge from pyramidal tract, which will support on designing individual treatment plan, reducing the incidence of complications, and improving long-term life quality in patients.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Imagem de Tensor de Difusão , Transtornos Motores/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Motores/complicações , Força Muscular , Cuidados Pré-Operatórios/métodos , Tratos Piramidais/lesões , Tratos Piramidais/cirurgia , Qualidade de Vida , Resultado do TratamentoRESUMO
Intracerebral hemorrhage (ICH) is one of the most severe subtypes of stroke with high morbidity and mortality. Although a lot of drug discovery studies have been conducted, the drugs with satisfactory therapeutic effects for motor paralysis after ICH have yet to reach clinical application. Transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable cation channel and activated by hypoosmolarity and warm temperature, is expressed in various cell types. The present study investigated whether TRPV4 would participate in the brain damage in a mouse model of ICH. ICH was induced by intrastriatal treatment of collagenase. Administration of GSK1016790A, a selective TRPV4 agonist, attenuated neurological and motor deficits. The inhibitory effects of the TRPV4 agonist in collagenase-injected WT mice were completely disappeared in TRPV4-KO mice. The TRPV4 agonist did not alter brain injury volume and brain edema at 1 and 3 days after ICH induction. The TRPV4 agonist did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 3 days after ICH induction. Quantitative RT-PCR experiments revealed that the TRPV4 agonist significantly upregulated the expression level of c-fos, a marker of neuronal activity, while the agonist gave no effects on the expression level of cytokines/chemokines at 1 day after ICH induction, These results suggest that stimulation of TRPV4 would ameliorate ICH-induced brain injury, presumably by increased neuronal activity and TRPV4 provides a novel therapeutic target for the treatment for ICH.
Assuntos
Hemorragia Cerebral/complicações , Leucina/análogos & derivados , Transtornos Motores/prevenção & controle , Doenças do Sistema Nervoso/prevenção & controle , Sulfonamidas/farmacologia , Canais de Cátion TRPV/agonistas , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Hemorragia Cerebral/induzido quimicamente , Colagenases , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Leucina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transtornos Motores/etiologia , Doenças do Sistema Nervoso/etiologia , Proteínas Proto-Oncogênicas c-fos/genética , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
OBJECTIVE: The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy. METHODS: This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. SETTINGS ARE URBAN: Urban and rural areas surrounding 2 academic medical centers. There will be 90 preterm infants enrolled in this study born at <29 weeks of gestation. SPEEDI is a developmental intervention provided by collaboration between a physical therapist and parent to support a child's motor and cognitive development. The primary outcome measure is the Bayley Scale of Infant and Toddler Development Cognitive and Gross Motor Scaled Scores. Secondary measures include behavioral coding of early problem solving skills, the Gross Motor Function Measure, and Test of Infant Motor Performance. IMPACT: More than 270,000 infants are born very preterm in the United States each year, 50% of whom will have neurological dysfunction that limits their ability to keep pace with peers who are typically developing. This study is a step toward understanding the impact that intensive developmental intervention could have in this population in the first months of life.
Assuntos
Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/prevenção & controle , Intervenção Médica Precoce/métodos , Terapia por Exercício/métodos , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Ludoterapia/métodos , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/reabilitação , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Transtornos Motores/prevenção & controle , Destreza Motora/fisiologia , Resolução de Problemas , Fatores de TempoRESUMO
RESUMO O objetivo deste estudo foi avaliar o desenvolvimento motor de crianças de quatro a 17 meses e investigar sua associação com fatores de risco sociodemográficos. Estudo transversal, descritivo, composto por crianças de quatro a 17 meses provenientes da unidade de internação pediátrica de um hospital público de Porto Alegre (RS), clinicamente estáveis e com alta breve prevista. Para a avaliação dos fatores de risco sociodemográficos foi utilizado um questionário elaborado pelas pesquisadoras, que abordou fatores biológicos, sociais e ambientais. Para a avaliação do desenvolvimento motor foi utilizada a Alberta Infant Motor Scale na versão traduzida, adaptada e validada para a população brasileira. Para a análise estatística foi utilizado o teste t de Student e o teste qui-quadrado, com nível de significância de 5% (p≤0,05). De um total de 110 crianças avaliadas, o desempenho motor se mostrou aquém do esperado em mais da metade delas (63,6%, n=70). Houve associação estatisticamente significativa entre o desenvolvimento motor e vacinas atrasadas (p=0,005), convivência com tabagistas em casa (p=0,047) e recebimento de benefício socioeconômico (p=0,036). Conclui-se que esses fatores sociais podem estar associados a fatores de risco ao desenvolvimento motor de crianças de quatro a 17 meses.
RESUMEN El presente estudio tuvo el objetivo de evaluar el desarrollo motor de niños de 4 a 17 meses de edad e investigar su asociación con factores de riesgo sociodemográficos. Es un estudio transversal, descriptivo, en el cual participaron niños de 4 a 17 meses de la unidad de hospitalización pediátrica de un hospital público en Porto Alegre (Brasil), clínicamente estables y con la espera de recibir el alta pronto. Para la evaluación de los factores de riesgo sociodemográficos, se utilizó un cuestionario desarrollado por los investigadores, que abordó los factores biológicos, sociales y ambientales. Para la evaluación del desarrollo motor, se utilizó la Alberta Infant Motor Scale en la versión traducida, adaptada y validada para la población brasileña. En el análisis estadístico, se aplicaron la prueba t de Student y la prueba chi-cuadrado, con un nivel de significación del 5% (p≤0,05). De 110 niños evaluados, más de la mitad de ellos (63,6%, n=70) tuvieron rendimiento motor inferior a lo esperado. Hubo una asociación estadísticamente significativa entre el desarrollo motor y las vacunas tardías (p=0,005), la convivencia con fumadores en el hogar (p=0,047) y el recibimiento de beneficios socioeconómicos (p=0,036). Se concluye que estos factores sociales pueden estar asociados con factores de riesgo para el desarrollo motor de niños de 4 a 17 meses.
ABSTRACT This study aimed to evaluate the motor development of children aged four to 17 months and investigate its association with sociodemographic risk factors. This is a cross-sectional descriptive study conducted with clinically stable children aged four to 17 months from the pediatric inpatient unit of a public hospital in Porto Alegre, RS, and whose hospital discharge would happen soon. For the evaluation of sociodemographic risk factors, a questionnaire developed by the researchers was used which addressed biological, social and environmental factors. The Alberta Infant Motor Scale (AIMS), in its version translated, adapted and validated to Brazilian Portuguese, was used in the evaluation of motor development. In statistical analysis, Student's t-test and Chi-square test were used with significance level of 5% (p≤0.05) for all tests. From a total of 110 evaluated children, motor performance was lower than expected in more than half of them (63.6%, n=70). Motor development presented statistically significant associations with delayed vaccines (p=0.005), cohabitation with smokers (p=0.047), and receiving socioeconomic benefits (p=0.036). In conclusion, social factors such as delayed vaccines, cohabitation with smokers and receiving socioeconomic benefits may be associated with risk factors related to motor development of children aged four months to 17 months old.
Assuntos
Humanos , Masculino , Feminino , Lactente , Desenvolvimento Infantil , Vulnerabilidade Social , Destreza Motora/fisiologia , Fatores Socioeconômicos , Poluição por Fumaça de Tabaco , Deficiências do Desenvolvimento/prevenção & controle , Deficiências do Desenvolvimento/reabilitação , Deficiências do Desenvolvimento/epidemiologia , Epidemiologia Descritiva , Estudos Transversais , Inquéritos e Questionários , Fatores de Risco , Transtornos Motores/diagnóstico , Transtornos Motores/prevenção & controle , Transtornos Motores/reabilitação , Transtornos Motores/epidemiologiaRESUMO
The Na leak-current channel (NALCN) regulates the resting membrane potential in excitable cells, thus determining the likelihood of depolarization in response to incoming signals. Gain-of-function (gf) mutations in this channel are associated with severe dystonic movement disorders in man. Currently, there are no known pharmacological antagonists or selective modulators of this important channel. A gain-of-function mutation in NALCN of C. elegans [known as unc-77(e625)] causes uncoordinated, hyperactive locomotion. We hypothesized that this hyperactive phenotype can be rescued with pharmacological modulators. Here, we summarize the results of targeted drug screening aimed at identification of drugs that corrected locomotion deficits in unc-77(e625) animals. To assay hyperactive locomotion, animals were acutely removed from food and characteristic foraging movements were quantified. Drug screening revealed that 2-aminoethoxydiphenyl borate (2-ABP), nifedipine, nimodipine, flunarizine and ethoxzolamide significantly decreased abnormal movements in unc-77(e625) animals. 2-APB also corrected egg release and coiling deficits in this strain. In addition, serotonin and dopamine both reduced hyperactive locomotion, consistent with regulatory interactions between these systems and the NALCN. 2-APB induced movement phenotypes in wild-type animals that faithfully mimicked those observed in NALCN knockout strains, which suggested that this drug may directly block the channel. Moreover, 2-APB and flunarizine showed significant structural similarities suggestive of overlap in their mode of action. Together, these studies have revealed new insights into regulation of NALCN function and led to the discovery of a potential pharmacological antagonist of the NALCN.
Assuntos
Proteínas de Caenorhabditis elegans/genética , Distonia/genética , Mutação com Ganho de Função/efeitos dos fármacos , Canais Iônicos/genética , Transtornos Motores/prevenção & controle , Animais , Compostos de Boro , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Etoxzolamida/farmacologia , Flunarizina/farmacologia , Técnicas de Inativação de Genes , Nifedipino/farmacologia , Nimodipina/farmacologia , Fenótipo , Canais de SódioRESUMO
The motor features in Parkinson's disease (PD) are associated with the degeneration of dopaminergic cells in the substantia nigra in the brain. Thus, the gold-standard in PD therapeutics still consists of dopamine replacement with levodopa. However, as the disease progresses, this therapeutic option becomes less effective and can be accompanied by levodopa-induced complications. On the other hand, several other neuronal pathways have been implicated in the pathological mechanisms of PD. In this context, the development of alternative therapeutic options that modulate non-dopaminergic targets is emerging as a major goal in the field. In a phenotypic-based screen in a zebrafish model of PD, we identified tapentadol as a candidate molecule for PD. The therapeutic potential of an agent that modulates the opioid and noradrenergic systems has not been explored, despite the implication of both neuronal pathways in parkinsonism. Therefore, we assessed the therapeutic properties of this µ-opioid receptor agonist and norepinephrine reuptake inhibitor in the 6-hydroxydopamine mouse model of parkinsonism. We further submitted 6-hydroxydopamine-lesioned mice to chronic treatment with levodopa and evaluated the effects of tapentadol during levodopa OFF states and on levodopa-induced dyskinesia. Importantly, we found that tapentadol halted the aggravation of dyskinesia and improved the motor impairments during levodopa OFF states. Altogether, our findings raise the hypothesis that concomitant modulation of µ-opioid receptor and norepinephrine transporter might constitute relevant intervention strategies in PD and that tapentadol holds therapeutic potential that may be translated into the clinical practice.
Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Modelos Animais de Doenças , Discinesia Induzida por Medicamentos/prevenção & controle , Transtornos Motores/prevenção & controle , Transtornos Parkinsonianos/prevenção & controle , Tapentadol/uso terapêutico , Animais , Discinesia Induzida por Medicamentos/fisiopatologia , Levodopa/toxicidade , Masculino , Camundongos , Transtornos Motores/induzido quimicamente , Transtornos Motores/fisiopatologia , Oxidopamina/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologiaRESUMO
BACKGROUND: Penetrating traumatic brain injury induces chronic inflammation that drives persistent tissue loss long after injury. Absence of endogenous reparative neurogenesis and effective neuroprotective therapies render injury-induced disability an unmet need. Cell replacement via neural stem cell transplantation could potentially rebuild the tissue and alleviate penetrating traumatic brain injury disability. The optimal transplant location remains to be determined. METHODS: To test if subacute human neural stem cell (hNSC) transplant location influences engraftment, lesion expansion, and motor deficits, rats (n = 10/group) were randomized to the following four groups (uninjured and three injured): group 1 (Gr1), uninjured with cell transplants (sham+hNSCs), 1-week postunilateral penetrating traumatic brain injury, after establishing motor deficit; group 2 (Gr2), treated with vehicle (media, no cells); group 3 (Gr3), hNSCs transplanted into lesion core (intra); and group 4 (Gr4), hNSCs transplanted into tissue surrounding the lesion (peri). All animals were immunosuppressed for 12 weeks and euthanized following motor assessment. RESULTS: In Gr2, penetrating traumatic brain injury effect manifests as porencephalic cyst, 22.53 ± 2.87 (% of intact hemisphere), with p value of <0.0001 compared with uninjured Gr1. Group 3 lesion volume at 17.44 ± 2.11 did not differ significantly from Gr2 (p = 0.36), while Gr4 value, 9.17 ± 1.53, differed significantly (p = 0.0001). Engraftment and neuronal differentiation were significantly lower in the uninjured Gr1 (p < 0.05), compared with injured groups. However, there were no differences between Gr3 and Gr4. Significant increase in cortical tissue sparing (p = 0.03), including motor cortex (p = 0.005) was observed in Gr4 but not Gr3. Presence of transplant within lesion or in penumbra attenuated motor deficit development (p < 0.05) compared with Gr2. CONCLUSION: In aggregate, injury milieu supports transplanted cell proliferation and differentiation independent of location. Unexpectedly, cortical sparing is transplant location dependent. Thus, apart from cell replacement and transplant mediated deficit amelioration, transplant location-dependent neuroprotection may be key to delaying onset or preventing development of injury-induced disability. LEVEL OF EVIDENCE: Preclinical study evaluation of therapeutic intervention, level VI.
Assuntos
Lesões Encefálicas Traumáticas/terapia , Traumatismos Cranianos Penetrantes/terapia , Transtornos Motores/prevenção & controle , Células-Tronco Neurais/transplante , Neuroproteção , Animais , Encéfalo/citologia , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Modelos Animais de Doenças , Traumatismos Cranianos Penetrantes/complicações , Traumatismos Cranianos Penetrantes/patologia , Humanos , Masculino , Transtornos Motores/etiologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/patologia , Ratos , Transplante Heterólogo/métodosRESUMO
Pharmaceuticals and cell-based regenerative medicine for Parkinson's disease (PD) offer palliative relief but do not arrest the disease progression. Cell therapy has emerged as an experimental treatment, but current cell sources such as human umbilical cord blood (hUCB) stem cells display only partial recapitulation of mature dopaminergic neuron phenotype and function. Nonetheless, stem cell grafts ameliorate PD-associated histological and behavioral deficits likely through stem cell graft-secreted therapeutic substances. We recently demonstrated the potential of hUCB-derived plasma in enhancing motor capabilities and gastrointestinal function, as well as preventing dopaminergic neuronal cell loss, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) rodent model of PD. Recognizing the translational need to test in another PD model, we now examined here the effects of an intravenously transplanted combination of hUCB and plasma into the 6-hydroxydopamine (6-OHDA) lesioned adult rats. Animals received three separate doses of 4 × 106 hUCB cells with plasma beginning at 7 days after stereotaxic 6-OHDA lesion, then behaviorally and immunohistochemically evaluated over 56 days post-lesion. Whereas vehicle-treated lesioned animals exhibited the typical 6-OHDA neurobehavioral symptoms, hUCB and plasma-treated lesioned animals showed significant attenuation of motor function, gut motility, and nigral dopaminergic neuronal survival, combined with diminished pro-inflammatory microbiomes not only in the nigra, but also in the gut. Altogether these data support a regenerative medicine approach for PD by sequestering inflammation and neurotoxicity through correction of gut dysbiosis.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Microbioma Gastrointestinal , Inflamação/prevenção & controle , Intoxicação por MPTP/terapia , Fármacos Neuroprotetores/administração & dosagem , Medicina Regenerativa , Cordão Umbilical/citologia , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/citologia , Inflamação/etiologia , Inflamação/patologia , Intoxicação por MPTP/etiologia , Intoxicação por MPTP/patologia , Masculino , Transtornos Motores/etiologia , Transtornos Motores/patologia , Transtornos Motores/prevenção & controle , Ratos , Ratos Sprague-Dawley , Substância Negra/citologiaRESUMO
Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disease characterized by demyelination of the Central Nervous System. Immune cells activation and release of pro-inflammatory cytokines play a crucial role in the disease modulation, decisively contributing to the neurodegeneration observed in MS and the experimental autoimmune encephalomyelitis (EAE), the widely used MS animal model. Synthetic glucocorticoids, commonly used to treat the MS attacks, have controversial effects on neuroinflammation and cognition. We sought to verify the influence of dexamethasone (DEX) on the EAE progression and on EAE-induced cognitive deficits. In myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced EAE female mice, treated once with DEX (50 mg/kg) or not, on the day of immunization, DEX decreased EAE-induced motor clinical scores, infiltrating cells in the spinal cord and delayed serum corticosterone peak. At the asymptomatic phase (8-day post-immunization), DEX did not protected from the EAE-induced memory consolidation deficits, which were accompanied by increased glucocorticoid receptor (GR) activity and decreased EGR-1 expression in the hippocampus. Blunting hippocampal GR genomic activation with DnGR vectors prevented DEX effects on EAE-induced memory impairment. These data suggest that, although DEX improves clinical signs, it decreases cognitive and memory capacity by diminishing neuronal activity and potentiating some aspects of neuroinflammation in EAE.
Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/tratamento farmacológico , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos Motores/etiologia , Transtornos Motores/prevenção & controle , Animais , Anti-Inflamatórios/farmacocinética , Corticosterona/sangue , Dexametasona/farmacocinética , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/diagnóstico , Imunofluorescência , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Motores/fisiopatologia , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
Green tea from Camellia sinensis plays a well-established neuroprotective role in several neurodegenerative diseases, including intracerebral hemorrhage (ICH). However, the other teas of the same plant do not have their properties well understood; but they can be as effective as green tea as an alternative therapy. In this study, we investigated the effects of supplementation with green tea and red tea from Camellia sinensis on motor deficits and striatum oxidative damage in rats submitted to hemorrhagic stroke (ICH). Male Wistar rats were supplemented with green tea, red tea, or vehicle for 10 days prior to ICH induction. After injury, the rats were submitted to motor tests (open field for locomotion, rotarod for balance, and neurological deficit scale (NDS)) 1, 3, and 7 days after ICH induction, while the tea supplementation was maintained. Subsequently, the rats were euthanized to striatal tissue dissection for biochemical analyzes (lipid peroxidation, reactive oxygen species, glutathione levels, and total antioxidant capacity). ICH caused locomotor and balance deficits, as well as increased the neurological deficit (NDS). Only red tea prevented locomotor deficits after injury. Green tea and red tea prevented balance deficits on the seventh day after ICH. On NDS evaluation, green tea presented a better neuroprotection than red tea (until day 3 after ICH injury). In addition, ICH increased reactive oxygen species and lipid peroxidation levels, without altering antioxidant markers. Green and red teas were effective in decreasing the lipid peroxidation levels. Therefore, green and red teas partially prevented the motor deficits and striatal oxidative damage induced by ICH. Based on our results, we can consider that the two teas seem to be equally effective to prevent motor deficits and striatal oxidative damage induced by hemorrhagic stroke in rats.
Assuntos
Corpo Estriado/efeitos dos fármacos , Hemorragias Intracranianas/complicações , Transtornos Motores/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Acidente Vascular Cerebral/complicações , Chá , Animais , Camellia sinensis , Corpo Estriado/metabolismo , Masculino , Transtornos Motores/etiologia , Extratos Vegetais/isolamento & purificação , Ratos WistarRESUMO
BACKGROUND CONTEXT: Intraoperative neurophysiological monitoring (IONM) has gained rather widespread acceptance as a method to mitigate risk to the lumbar plexus during lateral lumbar interbody fusion (LLIF) surgery. The most common approach to IONM involves using only electromyography (EMG) monitoring, and the rate of postoperative deficit remains unacceptably high. Other test modalities, such as transcranial electric motor-evoked potentials (tcMEPs) and somatosensory-evoked potentials, may be more suitable for monitoring neural integrity, but they have not been widely adopted during LLIF. Recent studies have begun to examine their utility in monitoring LLIF surgery with favorable results. PURPOSE: This study aimed to evaluate the efficacy of different IONM paradigms in the prevention of iatrogenic neurologic sequelae during LLIF and to specifically evaluate the utility of including tcMEPs in an IONM strategy for LLIF surgery. STUDY DESIGN/SETTING: A non-randomized, retrospective analysis of 479 LLIF procedures at a single institution over a 4-year period was conducted. During the study epoch, three different IONM strategies were used for LLIF procedures: (1) surgeon-directed T-EMG monitoring ("SD-EMG"), (2) neurophysiologist-controlled T-EMG monitoring ("NC-EMG"), and (3) neurophysiologist-controlled T-EMG monitoring supplemented with MEP monitoring ("NC-MEP"). PATIENT SAMPLE: The patient population comprised 254 men (53.5%) and 221 women (46.5%). Patient age ranged from a minimum of 21 years to a maximum of 89 years, with a mean of 56.6 years. OUTCOME MEASURES: Physician-documented physiological measures included manual muscle test grading of hip-flexion, hip-adduction, or knee-extension, as well as hypo- or hyperesthesia of the groin or anterolateral thigh on the surgical side. Self-reported measures included numbness or tingling in the groin or anterolateral thigh on the surgical side. METHODS: Patient progress notes were reviewed from the postoperative period up to 12 months after surgery. The rates of postoperative sensory-motor deficit consistent with lumbar plexopathy or peripheral nerve palsy on the surgical side were compared between the three cohorts. RESULTS: Using the dependent measure of neurologic deficit, whether motor or sensory, patients with NC-MEP monitoring had the lowest rate of immediate postoperative deficit (22.3%) compared with NC-EMG monitoring (37.1%) and SD-EMG monitoring (40.4%). This result extended to sensory deficits consistent with lumbar plexopathy (pure motor deficits being excluded); patients with NC-MEP monitoring had the lowest rate (20.5%) compared with NC-EMG monitoring (34.3%) and SD-EMG monitoring (36.9%). Additionally, evaluation of postoperative motor deficits consistent with peripheral nerve palsy (pure sensory deficits being excluded) revealed that the NC-MEP group had the lowest rate (5.7%) of motor deficit compared with the SD-EMG (17.0%) and NC-EMG (17.1%) cohorts. Finally, when assessing only those patients whose last follow-up was greater than or equal to 12 months (n=251), the rate of unresolved motor deficits was significantly lower in the NC-MEP group (0.9%) compared with NC-EMG (6.9%) and SD-EMG (11.0%). A comparison of the NC-MEP versus NC-EMG and SD-EMG groups, both independently and combined, was statistically significant (>95% confidence level) for all analyses. CONCLUSIONS: The results of the present study indicate that preservation of tcMEPs from the adductor longus, quadriceps, and tibialis anterior muscles are of paramount importance for limiting iatrogenic sensory and motor injuries during LLIF surgery. In this regard, the inclusion of tcMEPs serves to compliment EMG and allows for the periodic, functional assessment of at-risk nerves during these procedures. Thus, tcMEPs appear to be the most effective modality for the prevention of both transient and permanent neurologic injury during LLIF surgery. We propose that the standard paradigm for protecting the nervous system during LLIF be adapted to include tcMEPs.
Assuntos
Potencial Evocado Motor/fisiologia , Monitorização Neurofisiológica Intraoperatória/métodos , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletromiografia/métodos , Feminino , Humanos , Doença Iatrogênica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Transtornos Motores/etiologia , Transtornos Motores/prevenção & controle , Estudos Retrospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/prevenção & controle , Fusão Vertebral/efeitos adversos , Adulto JovemRESUMO
The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (pâ¯<â¯0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.
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Estimulação Encefálica Profunda , Maleato de Dizocilpina/farmacologia , Colículos Inferiores/efeitos dos fármacos , Colículos Inferiores/fisiologia , Intoxicação por MPTP , Transtornos Motores/prevenção & controle , Animais , Masculino , Camundongos , Microinjeções , Atividade Motora/efeitos dos fármacos , Transtornos Motores/induzido quimicamente , N-Metilaspartato/farmacologia , Teste de Desempenho do Rota-RodRESUMO
INTRODUCTION: Antenatal magnesium sulfate (MgSO4) administration has shown to be effective in minimizing cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIALS AND METHODS: A prospective cohort study was conducted on neonates of less than 32 weeks' gestation admitted to the neonatal intensive care unit of University Hospital Complex of Vigo from December 2012 to July 2015. Comparative analysis of magnesium levels between the groups of neonates exposed to MgSO4 and the control group. RESULTS: A total of 118 neonates were included in the study. The mothers of 62 of them had received MgSO4 as a neuroprotective agent. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24 hours of life (r2 = 0.397; p < 0.001). CONCLUSION: The MgSO4 dose received by the mother has a linear relationship with the magnesium levels obtained in neonates.
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Recém-Nascido Prematuro/sangue , Sulfato de Magnésio/uso terapêutico , Magnésio/sangue , Fármacos Neuroprotetores/uso terapêutico , Estudos de Casos e Controles , Paralisia Cerebral/prevenção & controle , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Lineares , Masculino , Transtornos Motores/prevenção & controle , Gravidez , Cuidado Pré-Natal/métodos , Estudos ProspectivosRESUMO
In several epidemiological studies, an association between pesticide exposure and the incidence of Parkinson's disease (PD) has been reported. Increasing evidence showed that oxidative stress plays an important role in the pathogenesis of PD. The present study investigated the preventive effect of crocin, saffron active components, on malathion (an organophosphate pesticide (OP))-induced Parkinson-like behaviors in rat. Rats were divided into eight groups: control (normal saline), malathion (100 mg/kg/day, i.p), crocin (10, 20, or 40 mg/kg/day, i.p) plus malathion, levodopa (10 mg/kg/day, i.p) plus malathion, crocin (40 mg/kg/day, i.p), and PEG (vehicle of levodopa) groups. Treatments were continued for 28 days. The neurobehavioral tests which include open field, rotarod and catalepsy were performed on day 28. The activity of acetylcholinesterase (AChE) in serum, the levels of malondialdehyde (MDA), reduced glutathione (GSH), TNF-α, and IL-6 in striatum at the end of treatments were evaluated. Results showed that malathion induced neurobehavioral impairments together with elevation of MDA, TNF-α and IL-6 levels, reduction of GSH, and AChE activity. Crocin (10, 20, and 40 mg/kg) improved neurobehavioral impairments induced by malathion but not AChE activity. Crocin (10, 20, and 40 mg/kg) or levodopa plus malathion decreased MDA and increased GSH. Also crocin (10 mg/kg) decreased TNF-α and IL-6 levels in striatum. In summary, subchronic malathion exposure induced Parkinson-like behavior in rat. Crocin exhibited protective effects against malathion-induced Parkinson-like behavior through reducing lipid peroxidation, improvement of motor deficit and anti-inflammatory effects.