Este trabalho foi financiado pela Fundação de ciência Natural de Beijing (No.7162124) e Xin-ao Fundação para a Universidade de Beijing de medicina chinesa.

Todos os animais foram mantidos em conformidade com as diretrizes da legislação chinesa sobre o uso ético e cuidar de animais de laboratório.
1. pré-modelagem preparação
<ol><li>
Preparação do laboratório
	<ol>
<li>Execute a lâmpada de UV durante pelo menos 30 min antes do experimento.</li>
		<li>Controle a temperatura do laboratório a 25 ± 3 ° C e umidade relativa em torno de 30%.</li>
		<li>Ligue o laboratório luz às 06:00 e desligar às 18:00 para estabelecer um ciclo claro/escuro de 12 h/12 h.</li>
	</ol>
</li>
	<li>
Construção de caixa de plataforma múltipla
	<ol>
<li>Construa um depósito de plástico opaco sem uma cobertura de 110 × 60 × 40 cm3.</li>
		<li>Corrigir a quinze plataformas circulares (h = 8 cm, d = 6,5 cm) na parte inferior do tanque, o enfermeiro que distribuir em três linhas e cinco colunas. Deixe espaço suficiente entre cada plataforma, mais ou menos 10 cm entre colunas e entre linhas de 13 centímetros.</li>
		<li>Definir uma saída de água no lado lateral do tanque e instalar uma torneira.</li>
		<li>Fazer uma cobertura de rede de fio de ferro para o tanque com uma caixa de comida pendurado nela.</li>
	</ol>
</li>
	<li>
Agrupamento e ratos de habitação Nota: Ratos machos Wistar de 8 semanas de idade, pesando aproximadamente 200-210 g, são utilizados no experimento. Os ratos vivem em grupos durante o processo de modelagem.<ol>
<li>Número de raízes de cauda dos ratos com uma caneta.</li>
		<li>Pesar os ratos, excluir o extremamente leve ou mais pesada e dividir o resto aleatoriamente em grupos de controle e modelo.</li>
		<li>Delicadamente colocou os ratos as gaiolas limpas e permitir-lhes para se aclimatar ao laboratório pelo menos 3 dias. Fornece água suficiente e fornecimento de alimentos.</li>
	</ol>
</li>
</ol>2. modelagem com MMPM
Nota: O processo começa às 18:00 e termina às 08:00 no dia seguinte, para um total de 14 h por dia, durante 21 dias. Para evitar fatores de interferência, a mesma pessoa é necessária para conduzir todo o experimento, enquanto usava o mesmo casaco de laboratório. 10 ratos Wistar são usados no experimento.
<ol><li>Coloque o reservatório sobre uma superfície plana, por exemplo, no chão. Em seguida, encha o reservatório com aproximadamente 7 cm de água morna (25 ± 3 ° C), cerca de 1 cm abaixo da plataforma plana.</li>
	<li>Prepare comida e bebida suficiente para todos os ratos no tanque para 1 dia. Forragem e água colocaram na caixa de comida e pendurá-lo na capa. Nota: Alguns ratos inteligentes aprendem a descansar na caixa de comida. Em caso afirmativo, conduzi-los a volta para o tanque.</li>
	<li>Levar os ratos do grupo de modelo fora da gaiola, agarrá-los pelo rabo e colocá-los suavemente para o tanque. Lançar todos os ratos na água em vez das plataformas para motivar o seu medo de água. Certifique-se de que todos os ratos Obtém uma plataforma para se sustentar, enquanto ratos do grupo controle permanecer em suas gaiolas originais com comida e água suficientes.</li>
	<li>Tampa do tanque. Monitore os ratos para evitar ferimento acidental. Se um rato permanece na água por mais de 1h sem subir na plataforma, buscá-lo fora do tanque e removê-lo do teste.</li>
	<li>Após 14 h, tirar os ratos do modelo do tanque e seque os cabelos com um secador. Re-marca as caudas dos ratos se desvanece-se. Retornar os ratos para suas gaiolas originais e fornecer-lhes comida e água suficientes.</li>
	<li>Limpe todos os cantos do aquário. Elevar um lado do tanque e abra a torneira para a água de esgoto de saída.</li>
	<li>Esterilizar o tanque com um spray de etanol 75% e expô-lo à luz UV.</li>
</ol>3. modelo de avaliação: Teste comportamental
Nota: Todos os testes são realizados no laboratório comportamental. Ruído e luz extra não são permitidas durante o teste para evitar a perturbação. Se possível, use o mesmo pessoa (s) para realizar cada teste. Um casaco escuro e luvas são necessárias para o reconhecimento de escala de cinza no processamento de imagem. Executar o OFT primeiro como tem o menor efeito sobre o comportamento do rato.
<ol><li>
OFT
	<ol>
<li>Verifique se o gravador sobre a caixa de campo aberto para se certificar que está ligado à estação de trabalho e cobre cada canto da caixa. Ajuste a iluminação para eliminar sombras na caixa.</li>
		<li>Mova os ratos em laboratório comportamental em suas gaiolas originais. Permita-lhes para se aclimatar pelo menos 1 h antes do teste.</li>
		<li>Limpar e desinfetar a caixa com 75% de etanol para garantir que não há nenhum excremento ou cheiro do experimento anterior.</li>
		<li>Remover um rato da gaiola por suas costas e colocá-lo suavemente na área central da caixa. Rapidamente os braços retiro da caixa para não bloquear o tiro.</li>
		<li>Entrada de número de ratos e iniciar a gravação. Contagem e registro da frequência de atividades verticais, como o rato, incluindo a criação e a escalada.</li>
		<li>Depois de 5 min, parar a gravação, tira da caixa com o rato e devolvê-lo para a gaiola.</li>
		<li>Repita as etapas 3.1.3 - 3.1.6 até que todos os ratos terminaram o teste.</li>
	</ol>
</li>
	<li>
EPM
	<ol>
<li>Execute as etapas de pré-seleção e aclimatação quanto o OFT (etapas 3.1.1 - 3.1.2).</li>
		<li>Remover um rato da gaiola por suas costas e colocá-lo suavemente sobre a parte de junção dos dois braços. Aterrar o rato para o braço esquerdo aberto e sair rapidamente para não bloquear o tiro.</li>
		<li>Entrada de número de ratos e iniciar a gravação. Contagem e registo a frequência de entradas diferentes de braço. Se o rato cai fora do labirinto no teste, buscá-lo e enviá-lo para o labirinto. Gravar informações detalhadas para análise de dados.</li>
		<li>Depois de 5 min, parar a gravação, pegue o rato fora e devolvê-lo para a gaiola.</li>
		<li>Remover o excremento e limpe o labirinto com 75% de etanol para eliminar cheiro do antigo rato.</li>
		<li>Repita as etapas 3.2.2 - 3.2.5 até que todos os ratos terminaram o teste.</li>
	</ol>
</li>
	<li>
Teste de ES
	<ol>
<li>Encha o tanque de natação (70 × 30 × 110 cm3) com 80 cm de água morna (25 ± 3 ° C). Nota: Se houver um termostato no tanque, temperatura da água deve ser definida em 37 ° C, que é semelhante à temperatura do corpo do rato. Caso contrário, defina-o como a temperatura para mantê-la constante.</li>
		<li>Faça uma carga para cada rato com pino cachos e amarrá-lo suavemente na sua raiz da cauda. A carga pesa 10% do peso do rato.</li>
		<li>Pegar um rato pela cauda e jogá-lo no tanque de natação. Se os ratos huddle ou agarrar-se à parede, os distinguem e conduzi-los de volta na água.</li>
		<li>Iniciar a cronometragem no momento em que o rato é colocado em água e parar o tempo quando ele está esgotado, que é demonstrada como a incapacidade de lutar fora da água com a boca e o nariz por baixo da água por mais de 10 s. Nota: Às vezes, exaustão e afogamento ocorrem de repente. Certifique-se de ter bastante experimentadores para gravar e salvar o animal ao mesmo tempo.</li>
		<li>Remova os ratos exaustos fora da água sem interromper os outros. Seque os cabelos, re-marcar seus números e enviá-los de volta para a gaiola.</li>
		<li>Mude a água no tanque após conclusão de um grupo. Depois de fazem todos os ratos, esvaziar o tanque de natação e limpar e esterilizá-lo com etanol e luz UV.</li>
	</ol>
</li>
</ol>4. modelo de avaliação: Deteção de neurotransmissor Central
<ol><li>Anestesia o rato com injeção intra-peritoneal de hidrato de cloral 10% (3ml/kg) até que esteja inconsciente.</li>
	<li>Decapitar o rato.</li>
	<li>Faça uma incisão longitudinal ao longo da linha pós-medial, abrir o crânio para ambos os lados e expor o cérebro. Vire o crânio, remover o cérebro e colocar o cérebro em um saco de gelo.</li>
	<li>Separar e remover o hipotálamo, que é a área em forma de diamante na parte central da base do cérebro que tem uma fronteira clara com tecidos circundantes. Coloque-o em um tubo estéril e congelá-lo com nitrogênio líquido. Armazene todas as amostras em um frigorífico de-80 ° C.</li>
	<li>Detecta o conteúdo da DA e 5-HT no hipotálamo usando cromatografia líquida de alto desempenho (HPLC)8.</li>
</ol>

<ol>
	<li>Ishii, A., Tanaka, M., Yamano, E., Watanabe, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neural+substrates+of+physical+fatigue+sensation+to+evaluate+ourselves:+a+magnetoencephalography+study.">The neural substrates of physical fatigue sensation to evaluate ourselves: a magnetoencephalography study.</a> Neuroscience. 261, 60-67 (2014).</li><li>Dalsgaard, M. K., Secher, N. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Brain+at+Work:+A+Cerebral+Metabolic+Manifestation+of+Central+Fatigue?.">The Brain at Work: A Cerebral Metabolic Manifestation of Central Fatigue?.</a> Journal of Neuroscience Research. 85 (15), 3334-3339 (2007).</li><li>Chaudhuri, A., Behan, P. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fatigue+in+neurological+disorders.">Fatigue in neurological disorders.</a> The Lancet. 363, 978-988 (2004).</li><li>Baston, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise-induced+central+fatigue:+a+review+of+the+literature+with+implications+for+dance+science+research.">Exercise-induced central fatigue: a review of the literature with implications for dance science research.</a> Journal of Dance Medicine &amp; Science. 17 (2), 53-62 (2013).</li><li>Yamashita, M., Yamamoto, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tryptophan+and+Kynurenic+Acid+May+Produce+an+Amplified+Effect+in+Central+Fatigue+Induced+by+Chronic+Sleep+Disorder.">Tryptophan and Kynurenic Acid May Produce an Amplified Effect in Central Fatigue Induced by Chronic Sleep Disorder.</a> International Journal of Tryptophan Research. 7, 9-14 (2014).</li><li>Lee, S. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+duration+of+one+bout+treadmill+exercise+on+cell+proliferation+and+central+fatigue+in+rats.">The impact of duration of one bout treadmill exercise on cell proliferation and central fatigue in rats.</a> Journal of Exercise Rehabilitation. 9 (5), 463-469 (2013).</li><li>Su, k. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rutin,+a+flavonoid+and+principal+component+of+saussurea+involucrata,+attenuates+physical+fatigue+in+a+forced+swimming+mouse+model.">Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model.</a> International Journal of Medical Sciences. 11 (5), 528-537 (2014).</li><li>Hashemi, F., Laufer, R., Szegi, P., Csomor, V., Kal &#225;sz, H., Tekes, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HPLC+determination+of+brain+biogenic+amines+following+treatment+with+bispyridinium+aldoxime+K203.">HPLC determination of brain biogenic amines following treatment with bispyridinium aldoxime K203.</a> Acta Physiologica Hungarica. 101 (1), 40-46 (2014).</li><li>Machado, R. B., Hipo'lide, D. C., Benedito-Silva, A. A., Tufik, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+deprivation+induced+by+the+modified+multiple+platform+technique:+quantification+of+sleep+loss+and+recovery.">Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery.</a> Brain Research. 1004 (1-2), 45-51 (2004).</li><li>Alzoubi, K. H., Khabour, O. F., Tashtoush, N. H., AI-Azzam, S. I., Mhaidat, N. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+the+Effect+of+Pentoxifylline+on+Sleep-Deprivation+Induced+Memory+Impairment.">Evaluation of the Effect of Pentoxifylline on Sleep-Deprivation Induced Memory Impairment.</a> Hippocampus. 23 (9), 812-819 (2013).</li><li>Pires, G. N., Tufik, S., Andersen, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Grooming+analysis+algorithm:+Use+in+the+relationship+between+sleep+deprivation+and+anxiety-like+behavior.">Grooming analysis algorithm: Use in the relationship between sleep deprivation and anxiety-like behavior.</a> Progress in Neuro-Psychopharmacology and Biological Psychiatry. 41, 6-10 (2013).</li><li>Yamashita, M., Yamamoto, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+a+rat+model+of+central+fatigue+induced+by+chronic+sleep+disorder+and+excessive+brain+tryptophan.">Establishment of a rat model of central fatigue induced by chronic sleep disorder and excessive brain tryptophan.</a> Japanese Journal of Cognitive Neuroscience. 15, 67-74 (2013).</li><li>Arai, M., Yamazaki, M., Inoue, K., Fushiki, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+intracranial+injection+of+transforming+growth+factor-beta+relevant+to+central+fatigue+on+the+waking+electroencephalogram+of+rats+Comparison+with+effects+of+exercise.">Effects of intracranial injection of transforming growth factor-beta relevant to central fatigue on the waking electroencephalogram of rats Comparison with effects of exercise.</a> Progress in Neuro-Psychopharmacology and Biological Psychiatry. 26 (2), 307-312 (2002).</li><li>Han, C. X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+behavioral+and+brain+changes+after+different+durations+of+the+modified+multiple+platform+method+on+rats:+An+animal+model+of+central+fatigue.">Distinct behavioral and brain changes after different durations of the modified multiple platform method on rats: An animal model of central fatigue.</a> PloS One. 12 (5), e0176850 (2017).</li><li>Tang, X., Yang, L., Sanford, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Individual+variation+in+sleep+and+motor+activity+in+rats.">Individual variation in sleep and motor activity in rats.</a> Behavioural Brain Research. 180 (1), 62-68 (2007).</li><li>Stanford, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Open+Field+Test:+reinventing+the+wheel.">The Open Field Test: reinventing the wheel.</a> Journal of Psychopharmacology. 21 (2), 134-135 (2007).</li><li>Ahn, S. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Basal+anxiety+during+an+open+field+test+is+correlated+with+individual+differences+in+contextually+conditioned+fear+in+mice.">Basal anxiety during an open field test is correlated with individual differences in contextually conditioned fear in mice.</a> Animal Cells and Systems. 17 (3), 154 (2013).</li><li>Costa, A. A., Morato, S., Roque, A. C., Tin &#243;s, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+computational+model+for+exploratory+activity+of+rats+with+different+anxiety+levels+in+elevated+plus-maze.">A computational model for exploratory activity of rats with different anxiety levels in elevated plus-maze.</a> Journal of Neuroscience Methods. 236, 44-50 (2014).</li><li>Liu, Z., Wu, Y., Liu, T., Li, R., Xie, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Serotonin+regulation+in+a+rat+model+of+exercise-induced+chronic+fatigue.">Serotonin regulation in a rat model of exercise-induced chronic fatigue.</a> Neuroscience. 349, 27-34 (2017).</li><li>Foley, T. E., Fleshner, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroplasticity+of+dopamine+circuits+after+exercise:+implications+for+central+fatigue.">Neuroplasticity of dopamine circuits after exercise: implications for central fatigue.</a> NeuroMolecular Medicine. 10 (2), 67-80 (2008).</li><li>Leite, L. H., Rodrigues, A. G., Soares, D. D., Marubayashi, U., Coimbra, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+fatigue+induced+by+losartan+involves+brain+serotonin+and+dopamine+content.">Central fatigue induced by losartan involves brain serotonin and dopamine content.</a> Medicine &amp; Science in Sports &amp; Exercise. 42 (8), 1469-1476 (2010).</li></ol>

Os autores não têm nada para divulgar.

O MMPM é projetado originalmente por privação de sono9. Ratos são lançados em um tanque de água com plataformas fixadas na parte inferior. Impulsionado pelo medo instintivo de água, ratos permanecem em pé nas plataformas e ocorre sem dormir. O estudo mostra que diferentes horas de privação de sono levam a várias alterações no comportamento do rato e humor, incluindo reconhecimento de imparidade10en11e fadiga central. Alguns pesquisadores...

A fadiga é um dos principais fatores que ameaçam a saúde humana1. Nas últimas décadas, várias pesquisas provaram que fadiga é acionada por perifericamente mas centralmente orientada e sempre acompanhado com distúrbios emocionais e cognitivos. Fisiologista italiano Mosso r. proposto pela primeira vez a palavra fadiga Central2. Geralmente é definida como a actividade voluntária limitada e comprometimento da cognição devido à disfunção da transmissão do impulso no sistema nervoso central (SNC)3. Comparado com fadiga muscular periférica, fadiga central enfatiza alterações no SNC, bem como as consequentes perturbações emocionais/comportamentais, incluindo depressão, ansiedade, deficiência de cognição e perda de memória. Um estudo mostra que muitos fatores podem induzir a fadiga central, entre os quais excessiva atividade física e estresse mental, são imprescindíveis4. Quanto a patogênese, teorias como o triptofano-Quinurenina via hipótese5 explicar alterações em determinadas vias; no entanto, estudos mais aprofundados ainda são necessários para revelar as correlações central-periférico da fadiga central.
Como o mecanismo subjacente de fadiga central ainda não está claro, um modelo animal eficaz é muito importante para futuras pesquisas. Os modelos existentes de fadiga são principalmente induzidos por exercício excessivo, como escadas rolantes6 e natação peso carregado7, com pouca preocupação sobre fatores mentais. Para melhor simular o desenvolvimento da fadiga central, nosso grupo desenvolveu um modelo do rato com o MMPM. Durante o processo de modelagem, ratos permanecem em pé nas plataformas estreitas na caixa múltipla plataforma por longas horas, incluindo a parte do tempo de sono. Diferente dos modelos de exercício excessivo, o modelo MMPM usa a privação do sono parcial como um fator mental tendo em consideração a complexa patogênese da fadiga central.
Para avaliação do modelo, usamos os OFT e EPM testes para determinar o clima de ansiedade e voluntariado. O teste de ES é realizado para medir o desempenho muscular periférica. Além disso, tomamos o cérebro do rato e detectar a dopamina (DA) / conteúdo de serotonina (5-HT) em ambos os hypothalamuses para observar as diferenças de neurotransmissor central.
O protocolo apresentado abaixo destina-se à fadiga central de modelo induzida pela atividade física repetida e falta de sono, imitando uma condição comum na vida humana. No entanto, ao ajustar a duração do modelo, pode ser usada em muitos outros campos, como em estudos de observação e estresse do sono. No futuro, pesquisa, esperamos que este modelo vai ajudar a descobrir mais mudanças do CNS e sua conexão com o sistema periférico, para revelar o mecanismo de patogênese da fadiga central.

<table><tbody><tr><td>multiple platform sleep deprivation water tank</td><td>Customization,it is provided by the neuroimmunological laboratory of Beijing University of Chinese Medicine</td><td></td><td>110cm x 60cm x 40cm. There are 15 plastic small platforms at the bottom. The small platform is 6.5cm in diameter and 8cm high</td></tr><tr><td>Wistar rats</td><td>Beijing Weitong Lihua Experimental Animal Technology Company</td><td>license number SYXK (Beijing) 2016-0011</td><td>Use 32 Wistar healthy male rats ,8 week old (200-210 g)</td></tr><tr><td>Agilent 1100LC high performance liquid chromatograph&amp;nbsp;</td><td>Agilent</td><td>&amp;nbsp;G1379A, G1311A, G1313A , G1316A&amp;nbsp;</td><td>&amp;nbsp;G1379A, G1311A type chromatographic pump, G1313A automatic sampler, G1316A column temperature box</td></tr><tr><td>DECADE II SDC electrochemical detector</td><td>Dutch ANTEC company</td><td></td><td>glassy carbon electrode, Ag/AgCl reference electrode, workstations (Clarity CHS)</td></tr><tr><td>Biofuge Stratos high-speed refrigeration centrifuge</td><td>HERAEUS</td><td></td><td></td></tr><tr><td>VCX130 ultrasonic fracturing instrument</td><td>SONICS</td><td></td><td></td></tr><tr><td>ACS-ZEAS electronic scale</td><td>Phos technology development, Beijing.</td><td></td><td>The weight of the weighing rats can be accurate to 0.1g.</td></tr><tr><td>Open Field Box</td><td>Customization,it is provided by the neuroimmunological laboratory of Beijing University of Chinese Medicine</td><td></td><td>wooden box of open field&amp;nbsp; 100 cm by 100 cm x 40 cm, inside wall and bottom as the gray.The bottom is divided into 25 equal area squares, each of which is 20cm x 20cm, and the 16 grids along the outer wall are the external ones, and the other 9 grids are central.The camera is mounted above the median.</td></tr><tr><td>Elevated Plus-maze</td><td>Beijing zhongshi dechuang technology development co. LTD.</td><td></td><td>The open arms and close&amp;nbsp; arms of the cross are composed of 30cm x 5cm x 15cm, and the central area is 5cm x 5cm, with a camera mounted above the center and 45cm high.</td></tr><tr><td>rat swimming bucket.</td><td>Zhenhua biological instrument equipment co., LTD. Anhui,China.</td><td></td><td>The volume of plastic drum is 70cm x 30cm x 110cm, which is used for swimming in rats.</td></tr><tr><td>Thermometer</td><td>Shiya instrument co., LTD., changzhou,China.</td><td></td><td>Control water temperature</td></tr><tr><td>Small water pump</td><td>Xincheng technology co., LTD., chengdu,China.</td><td></td><td>Used for water tank and swimming behavior.</td></tr><tr><td>Ethovition3.0 behavioral software.</td><td>Nuldus,Netherlands</td><td></td><td>Measurement analysis of rat behavior videos.</td></tr></tbody></table>

a rat model of central fatigue using a modified multiple platform method

Neste artigo, apresentamos um modelo do rato de fadiga central usando o modificado método de plataforma múltipla (MMPM). A caixa de plataforma múltipla foi concebida como um tanque de água com plataformas estreitas na parte inferior. Os ratos do modelo foram colocados no tanque e ficou nas plataformas para 14 h (18:00-08:00) por dia por 21 dias consecutivos, com um grupo de controle em branco para contraste. No final da modelagem, ratos no grupo modelo mostraram uma aparência cansada óbvia. Para avaliar o modelo, realizamos vários testes comportamentais, incluindo o campo aberto (OFT), teste da elevada além de labirinto (EPM) e o teste de natação exaustiva (ES). Os resultados mostraram que essa ansiedade, comprometimento da cognição espacial, desempenho pobre do músculo e recusada atividade voluntária apresentado em ratos modelo confirmam o diagnóstico da fadiga central. Alterações de neurotransmissores a central também verificado o resultado. Em conclusão, o modelo simulado com êxito a fadiga central, e estudos futuros com o modelo podem ajudar a revelar o mecanismo patológico da doença.

Descrevemos um modelo do rato de fadiga central usando MMPM. 24 ratos Wistar são aleatoriamente divididos em grupo controle e o grupo modelo, com 12 ratos em cada grupo. O aparelho modelo é projetado como um tanque de água com plataformas estreitas na parte inferior (Figura 1). Ratos do modelo fique nas plataformas para 14 h por dia, incluindo o tempo de sono parcial, durante 21 dias (Figura 2).
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Watch this Scientific Journal Video about A Rat Model of Central Fatigue Using a Modified Multiple Platform Method at JoVE.com

A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

Aqui, apresentamos um protocolo para apresentar um modelo do rato de fadiga central usando o modificado método de plataforma múltipla (MMPM).

Um rato do modelo de fadiga Central usando um modificado método de plataforma múltipla

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed ...

a-rat-model-central-fatigue-using-modified-multiple-platform

Research

JoVE Journal

Neuroscience

9.0K visualizações.  Beijing University of Chinese Medicine. Aqui, apresentamos um protocolo para apresentar um modelo do rato de fadiga central usando o modificado método de plataforma múltipla (MMPM).

Vídeo: A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

A Mouse Model of Fatigue Induced by Peripheral Irradiation

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. Here we describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. With appropriate shielding, the irradiation targets the lower abdominal/pelvic region of the mouse, sparing the brain, in an effort to model radiation treatment received by individuals with pelvic cancers. We deliver an irradiation dose that is sufficient to induce fatigue-like behavior in mice, measured by voluntary wheel-running activity (VWRA), without causing obvious morbidity. Since wheel running is a normal, voluntary behavior in mice, its use should have little confounding effect on other behavioral tests or biological measures. Hence, wheel running can be used as a feasible outcome measure in understanding the behavioral and biological correlates of fatigue. CRF is a complex condition with frequent comorbidities, and likely has causes related both to cancer and its various treatments. The methods described in this paper are useful for investigating radiation-induced changes that contribute to the development of CRF and, more generally, to explore the biological networks that can explain the development and persistence of a peripherally-triggered but centrally-driven behavior like fatigue.

We describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. The selected non-lethal irradiation dose leads to a week-long reduction in voluntary wheel-running activity.

Um mouse modelo de fadiga induzida por irradiação periférica

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

Pesquisa do câncer

Force and Position Control in Humans - The Role of Augmented Feedback

During motor behaviour, humans interact with the environment by for example manipulating objects and this is only possible because sensory feedback is constantly integrated into the central nervous system and these sensory inputs need to be weighted in order meet the task specific goals. Additional feedback presented as augmented feedback was shown to have an impact on motor control and motor learning. A number of studies investigated whether force or position feedback has an influence on motor control and neural activation. However, as in the previous studies the presentation of the force and position feedback was always identical, a recent study assessed whether not only the content but also the interpretation of the feedback has an influence on the time to fatigue of a sustained submaximal contraction and the (inhibitory) activity of the primary motor cortex using subthreshold transcranial magnetic stimulation. This paper describes one possible way to investigate the influence of the interpretation of feedback on motor behaviour by investigating the time to fatigue of submaximal sustained contractions together with the neuromuscular adaptations that can be investigated using surface EMG. Furthermore, the current protocol also describes how motor cortical (inhibitory) activity can be investigated using subthreshold TMS, a method known to act solely on the cortical level. The results show that when participants interpret the feedback as position feedback, they display a significantly shorter time to fatigue of a submaximal sustained contraction. Furthermore, subjects also displayed an increased inhibitory activity of the primary cortex when they believed to receive position feedback compared when they believed to receive force feedback. Accordingly, the results show that interpretation of feedback results in differences on a behavioural level (time to fatigue) that is also reflected in interpretation-specific differences in the amount of inhibitory M1 activity.

Controlling an identical movement with position or force feedback results in different neural activation and motor behavior. This protocol describes how to investigate behavioral changes by looking at neuromuscular fatigue and how to evaluate motor cortical (inhibitory) activity using subthreshold TMS with respect to the interpretation of augmented feedback.

Controle força e posição em Seres Humanos - O papel do feedback Augmented

During motor behaviour, humans interact with the environment by for example manipulating objects and this is only possible because sensory feedback is ...

Comportamento

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

A esteira de fadiga de teste: Um ensaio simples, de alta taxa de transferência de Fadiga-like Comportamento para o Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

Sit-to-stand-and-walk from 120% Knee Height: A Novel Approach to Assess Dynamic Postural Control Independent of Lead-limb

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined.
Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center-of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control.
BCOM-COP distance is expressed with and without normalization to subjects&#39; leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability.

Here, we present a novel protocol to measure positional stability at key events during the sit-to-stand-to-walk using the center-of-pressure to the whole-body-center-of-mass distance. This was derived from the force platform and three-dimensional motion-capture technology. The paradigm is reliable and can be utilized for the assessment of neurologically compromised individuals.

Sit-to-stand-e-pé do 120% joelho Altura: uma nova abordagem para avaliar Dinâmica Postural Independente de Controlo de Chumbo-limb

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: ...

Measuring the Motor Aspect of Cancer-Related Fatigue using a Handheld Dynamometer

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.

Simple and accessible methods were developed to measure the motor aspect of cancer-related fatigue objectively and quantitatively. We describe, in detail, ways to administer the physical fatigue test using a simple handgrip device as well as methods to calculate fatigue indices.

Medindo o aspecto motor da fadiga relacionada ao câncer usando um dinamômetro portátil

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on ...

Revised and Neuroimaging-Compatible Versions of the Dual Task Screen

Dual task paradigms simultaneously assess motor and cognitive abilities, and they can detect subtle, residual impairments in athletes with recent mild traumatic brain injury (mTBI). However, past dual task paradigms have focused solely on lower extremity skills and have relied on cumbersome, expensive laboratory equipment - thus limiting their practicality for everyday mTBI evaluation. Subsequently, we developed the Dual Task Screen (DTS), which takes &#60;10 minutes to administer and score, uses low-cost portable equipment, and includes lower extremity (LE) and upper extremity (UE) subtasks. The purpose of this manuscript was twofold. First, we describe the administration protocol for the revised DTS, which we revised to address the limitations of the original DTS. Specifically, the revisions included additions of smart devices to acquire more detailed gait data and inclusion of single cognitive conditions to test for disrupted cognitive performance under dual task conditions. Importantly, the revised DTS is a measure intended for future clinical use, and we present representative results from three male athletes to illustrate the type of clinical data that can be acquired from the measure. Importantly, we have yet to evaluate the sensitivity and specificity of the revised DTS in athletes with mTBI, which is the next research initiative. The second purpose of this manuscript is to describe a neuroimaging-compatible version of the DTS. We developed this version so we could evaluate the neural underpinnings of single and dual task performance, for a better empirical understanding of the behavioral deficits associated with mTBI. Thus, this manuscript also describes the steps we took to enable simultaneous functional near-infrared spectroscopy (fNIRS) measurement during the DTS, along with how we acquired and completed first-level processing of the fNIRS data.

We developed the original Dual Task Screen (DTS) as a portable, low-cost measure that can evaluate athletes with sports-induced mild traumatic brain injury. We revised the original DTS for future clinical use and developed a neuroimaging-compatible version of the DTS to measure neural underpinnings of single and dual task performance.

Versões revisadas e compatíveis com neuroimagem da tela de tarefa dupla

Dual task paradigms simultaneously assess motor and cognitive abilities, and they can detect subtle, residual impairments in athletes with recent mild ...

Integrando VR e Biossensores para Avaliação Quantitativa de Movimento e Atividade Muscular

Setup for the Quantitative Assessment of Motion and Muscle Activity During a Virtual Modified Box and Block Test

The ability to move allows us to interact with the world. When this ability is impaired, it can significantly reduce one's quality of life and independence and may lead to complications. The importance of remote patient evaluation and rehabilitation has recently grown due to limited access to in-person services. For example, the COVID-19 pandemic unexpectedly resulted in strict regulations, reducing access to non-emergent healthcare services. Additionally, remote care offers an opportunity to address healthcare disparities in rural, underserved, and low-income areas where access to services remains limited. 
Improving accessibility through remote care options would limit the number of hospital or specialist visits and render routine care more affordable. Finally, the use of readily available commercial consumer electronics for at-home care can enhance patient outcomes due to improved quantitative observation of symptoms, treatment efficacy, and therapy dosage. While remote care is a promising means to address these issues, there is a crucial need to quantitatively characterize motor impairment for such applications. The following protocol seeks to address this knowledge gap to enable clinicians and researchers to obtain high-resolution data on complex movement and underlying muscle activity. The ultimate goal is to develop a protocol for remote administration of functional clinical tests. 
Here, participants were instructed to perform a medically-inspired Box and Block task (BBT), which is frequently used to assess hand function. This task requires subjects to transport standardized cubes between two compartments separated by a barrier. We implemented a modified BBT in virtual reality to demonstrate the potential of developing remote assessment protocols. Muscle activation was captured for each subject using surface electromyography. This protocol allowed for the acquisition of high-quality data to better characterize movement impairment in a detailed and quantitative manner. Ultimately, these data have the potential to be used to develop protocols for virtual rehabilitation and remote patient monitoring.

Autor em destaque: Aprimorando a reabilitação remota com realidade virtual e eletromiografia

The protocol described here aims to enhance the quantitative evaluation of upper limb deficits, with the goal of developing additional technology for remote assessment both in the clinic and at home. Virtual reality and biosensor technologies are combined with standard clinical techniques to provide insights into the functioning of the neuromuscular system.

Configuração para a avaliação quantitativa do movimento e da atividade muscular durante um teste virtual modificado de caixa e bloco

The ability to move allows us to interact with the world. When this ability is impaired, it can significantly reduce one's quality of life and ...

Engenharia

Determining The Electromyographic Fatigue Threshold Following a Single Visit Exercise Test

Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit more motor units which is associated with an increase in the EMG amplitude. Although different protocols have been used to estimate the EMG fatigue threshold they require multiple visits which are impractical for a clinical setting. Here, we present a protocol for estimating the EMG fatigue threshold for cycle ergometry which requires a single visit. This protocol is simple, convenient, and completed within 15-20 min, therefore, has the potential to be translated into a tool that clinicians can use in exercise prescription.

This protocol describes the electromyographic fatigue threshold which demarcates between nonfatiguing and fatiguing exercise workloads. This information could be used to develop a more individualized training program.

Determinar o limiar de fadiga eletromiográfica Após um teste de esforço única visita

Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit ...

Um rato do modelo de fadiga Central usando um modificado método de plataforma múltipla

Resumo

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