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OBJECTIVE: To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. METHODS: A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. RESULTS: The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). CONCLUSION: The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

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BACKGROUND: Previous studies have demonstrated that electrical stimulation of the cerebellar fastigial nucleus (FNS) can considerably decrease infarction volume and improve neurofunction restoration following cerebral ischemia. Nevertheless, the molecular mechanism of the neuroprotective effect of FNS is still vague. METHODS: In this study, we developed a rat model of ischemia/reperfusion that included 1 h FNS followed by reperfusion for 3, 6, 12, 24, and 72 h. The expression profile of molecular alterations in brain tissues was obtained by transcriptome sequencing at five different time points. The function and pathway of miRNA expression pattern and core genes were annotated by Allen Brain Atlas, STRING database and Cytoscape software, so as to explore the mechanism of FNS-mediated neuroprotection. RESULTS: The results indicated that FNS is associated with the neurotransmitter cycle pathway. FNS may regulate the release of monoamine neurotransmitters in synaptic vesicles by targeting the corresponding miRNAs through core Dlg4 gene, stimulate the Alternative polyadenylation (APA) incident's anti -apoptosis effect on the brain, and stimulate the interaction activation of neurons in cerebellum, cortex/thalamus and other brain regions, regulate neurovascular coupling, and reduce cerebral damage. CONCLUSION: FNS may activate neuronal and neurovascular coupling by regulating the release of neurotransmitters in synaptic vesicles through the methylation of core Dlg4 gene and the corresponding transcription factors and protein kinases, inducing the anti-apoptotic mechanism of APA events. The findings from our investigation offer a new perspective on the way brain tissue responds to FNS-driven neuroprotection.

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Isquemia Encefálica , MicroARNs , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Ratas , Núcleos Cerebelosos/fisiología , Perfilación de la Expresión Génica , Infarto de la Arteria Cerebral Media , Isquemia , Fármacos Neuroprotectores/farmacología , Ratas Sprague-Dawley

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BACKGROUND: Cognitive impairment is common in people travelling to high altitude. Oxiracetam and electrical stimulation of cerebellar fastigial nucleus may have beneficial impacts. This study was to investigate the effects of preconditioning with Oxiracetam or fastigial nucleus stimulation (FNS) on cognitive decline following the ascension to high altitude. METHODS: The study was conducted on 60 male military voluntary members who were divided into control group, Oxiracetam group, and fastigial nucleus stimulation group. Transcranial doppler sonography, auditory evoked potential, electroencephalogram (EEG), and cognitive assessments were performed. RESULTS: People could still suffer cognitive dysfunction at 4,000 m high altitude despite that they have lived at 1,800 m altitude for several years. The 4,000 m altitude environment also prolonged P300 and N200 latencies. Both Oxiracetam and FNS improved cognitive function, reduced the prolonged latencies of Event Related Potentials (P300 and N200), decreased the average velocity of brain arteries, and enhanced EEG power spectral entropy at 4,000 m altitude. CONCLUSIONS: Neurophysiological evidences suggest the underlying mechanism of cognitive impairments. Both Oxiracetam and FNS can reduce cognitive decline post arrival at high altitude. They could be a potential pretreatment method for cognitive dysfunction resulted from high altitude.

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Altitud , Núcleos Cerebelosos/fisiología , Cognición , Disfunción Cognitiva , Pirrolidinas/farmacología , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Cognición/efectos de los fármacos , Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/prevención & control , Electroencefalografía/métodos , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Voluntarios Sanos , Humanos , Masculino , Pruebas Neuropsicológicas , Nootrópicos/farmacología , Medicina Preventiva/métodos , Resultado del Tratamiento

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OBJECTIVE: Cerebellar fastigial nucleus stimulation (FNS) has been shown to protect against cerebral ischemic injury. Peroxisome proliferator activator receptor gamma (PPARγ) has been reported to cause neuroprotection in animal models of stroke. The present study was performed to explore the neuroprotective mechanisms of FNS treatment in experimental stroke. METHODOLOGY: Adult male Sprague-Dawley (SD) rats preconditioned through transfection with either PPARγ-small hairpin RNA (shRNA) or lentiviral vector without shRNA and surgically subjected to middle cerebral artery occlusion and reperfusion subsequently received FNS treatment. The expression of PPARγ after FNS treatment was measured using western blotting and immunohistochemistry. Subsequently, the neuronal apoptosis, neurological deficits scores, and cerebral infarction were also evaluated. Additionally, the influence of FNS on the pro-inflammatory cytokines expression were determined by ELISA. RESULTS: We found that FNS significantly upregulated PPARγ expression, attenuated apoptosis and inflammatory response, and reduced infarct volume. The protective effect of FNS was abrogated by PPARγ-shRNA. CONCLUSION: Our results as described above suggested that FNS confers neuroprotection by upregulated PPARγ.

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Isquemia Encefálica/complicaciones , Núcleos Cerebelosos/fisiología , Estimulación Eléctrica , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/prevención & control , PPAR gamma/metabolismo , Regulación hacia Arriba/fisiología , Análisis de Varianza , Animales , Apoptosis/fisiología , Isquemia Encefálica/terapia , Modelos Animales de Enfermedad , Encefalitis/metabolismo , Ensayo de Inmunoadsorción Enzimática , Etiquetado Corte-Fin in Situ , Infarto de la Arteria Cerebral Media/complicaciones , Masculino , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Reperfusión , Transducción Genética

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Previous studies have shown that fastigial nucleus stimulation (FNS) reduces tissue damage resulting from focal cerebral ischemia. Although the mechanisms of neuroprotection induced by FNS are not entirely understood, important data have been presented in the past two decades. MicroRNAs (miRNAs) are a newly discovered group of non-coding small RNA molecules that negatively regulate target gene expression and are involved in the regulation of cell proliferation and cell apoptosis. To date, no studies have demonstrated whether miRNAs can serve as mediators of the brain's response to FNS, which leads to endogenous neuroprotection. Therefore, this study investigated the profiles of FNS-mediated miRNAs. Using a combination of deep sequencing and microarray with computational analysis, we identified a novel miRNA in the rat ischemic cortex after 1 h of FNS. This novel miRNA (PC-3p-3469_406), herein referred to as rno-miR-676-1, was upregulated in rats with cerebral ischemia after FNS. In vivo observations indicate that this novel miRNA may have antiapoptotic effects and contribute to neuroprotection induced by FNS. Our study provides a better understanding of neuroprotection induced by FNS. MicroRNA (miRNA) is defined as a small non-coding RNA that fulfills both the expression and biogenesis criteria. Here, we describe a novel miRNA in the rat ischemic cortex expressed after 1 h of fastigial nucleus stimulation (FNS). The miRNA was functionally characterized by secondary structure, quantitative expression, the conservation analysis, target gene analysis, and biological functions. We consider rno-miR-676-1 to be a true microRNA and present evidence for its neuroprotective effects exerted after induction by FNS.

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Núcleos Cerebelosos/fisiología , Terapia por Estimulación Eléctrica , Infarto de la Arteria Cerebral Media/fisiopatología , MicroARNs/biosíntesis , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Etiquetado Corte-Fin in Situ , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

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AIMS: Studies showed fastigial nucleus stimulation (FNS) reduced brain damage, but the mechanisms of neuroprotection induced by FNS were not entirely understood; MicroRNAs are noncoding RNA molecules that regulate gene expression in a posttranscriptional manner, but their functional consequence in response to ischemia-reperfusion (IR) remains unknown. We investigated the role of microRNA-29c in the neuroprotection induced by FNS in rat. METHODS: The IR rat models were conducted 1 day after FNS. Besides, miR-29c antagomir (or agomir or control) was infused to the left intracerebroventricular 1 day before IR models were conducted. We detected differential expression of Birc2 mRNA (also Bak1mRNA and miR-29c) level among different groups by RT-qPCR. The differential expression of Birc2 protein (also Bak1 protein) level among different groups was surveyed via Western blot. The neuroprotective effects were assessed by infarct volume, neurological deficit, and apoptosis. RESULTS: MiR-29c was decreased after FNS. Moreover, miR-29c directly bound to the predicted 3'-UTR target sites of Birc2 and Bak1 genes. Furthermore, over-expression of miR-29c effectively reduced Birc2 (also Bak1) mRNA and protein levels, increased infarct volume and apoptosis, and deteriorated neurological outcomes, whereas down-regulation played a neuroprotective role. CONCLUSIONS: MiR-29c correlates with the neuroprotection induced by FNS by negatively regulating Birc2 and Bak1.

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Núcleos Cerebelosos/fisiología , Estimulación Encefálica Profunda/métodos , Proteínas Inhibidoras de la Apoptosis/metabolismo , MicroARNs/metabolismo , Accidente Cerebrovascular/terapia , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Análisis de Varianza , Animales , Proteína 3 que Contiene Repeticiones IAP de Baculovirus , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Infarto Encefálico/tratamiento farmacológico , Infarto Encefálico/etiología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Proteínas Inhibidoras de la Apoptosis/genética , Masculino , MicroARNs/antagonistas & inhibidores , Mutación/genética , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Oligonucleótidos Antisentido/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Proteína Destructora del Antagonista Homólogo bcl-2/genética

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@#Objective To explore oropharyngeal swallowing disorders with videofluoroscopic swallowing study (VFSS). Methods 16 patients with dysphagia accepted VFSS with 10 ml of thin barium meal (50% w/v), thick barium meal (270% w/v), biscuit coated with thick barium meal in single swallow. Their swallowing function was observed on the lateral and anterior/posterior planes, including: symmetry of pyriform sinuses, oral transit time, presence of pharyngeal delay, pharyngeal transit time, oral and pharyngeal residue, and presence of aspiration.Results 5 patients demonstrated oral swallowing disorder. 3 patients demonstrated pharyngeal swallowing disorders, that was pharyngeal delay which caused in aspiration after swallowing. 8 patients demonstrated oropharyngeal swallowing disorders, and 3 of them presented aspiration,2 patients were silent aspirators, 1 was aspiration before and 1 after swallowing. The aspiration time could not be judged from the videofluoroscopy in the other one. For 4 patients with aspiration, 3 were severe, with more than 25% of the bolus aspirated, and 1 aspirated less than 5%. Conclusion VFSS can be helpful to plan individual rehabilitation.

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@#Objective To observe the of changes of cerebral blood flow and electroencephalography in chronic cerebral circulation insufficiency (CCCI) treated with fastigial nucleus stimulation (FNS) and hyperbaric oxygen (HBO). Methods 144 cases of CCCI were divided into 4 groups: 36 cases were treated with FNS and HBO, 36 cases with FNS, 36 cases with HBO, 36 cases without any treatment as control group. The blood velocity of anterior, middle, posterior cerebral arteries, vertebral artery and basilar artery were measured with transcranial Doppler (TCD) and the brain waves （α, β, δ, θ） were recorded with electroencephalography (EEG) before and after the treatment. Results Compared with the control, the brain blood velocity and α wave increased in all the treatment groups, especially in the HBO+FNS group, while β, δ, θ waves decreased (P<0.05). Conclusion FNS and HBO can increase cerebral blood flow and improve the cerebral function respectively.

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@#Objective To explore the effect of cerebellar fastigial nucleus stimulation (FNS) on the expression of Nestin in adult Wistar rat brain after focal cerebral ischemia/reperfusion.MethodsThe animal model of focal cerebral ischemia/reperfusion was made by filament occlusion of the right middle cerebral artery. 180 male Wistar rats were randomly divided into five groups: normal control group (NC group), sham operation control group (SC group), ischemia/reperfusion group (I/R group), ischemia/reperfusion treated with sham FNS group (I/RFs group), and ischemia/reperfusion treated with FNS group (I/RF group), each group contain 1 d, 3 d, 7 d, 14 d, 21 d and 28 d six time points (for each point, n=6). Immunohistochemistry method was used to detect the number of Nestin expression positive cells following various time and interference in lateral cerebral ventriculus and hippocampus in adult Wistar rat brain.ResultsAfter focal cerebral ischemia/reperfusion, the number of Nestin positive cells increased at each time point, reached small peak value in 7th d ( P<0.01). After treated with FNS, the number of Nestin positive cells increased more strikingly at each time point ( P<0.05, P<0.01), reached higher peak value in 7th d ( P<0.01), and maintained at higher level in 14th d. Furthermore, the shape of Nestin positive cells changed significantly.ConclusionFNS can increase the number of Nestin positive cells in some brain regions after focal cerebral ischemia/reperfusion.

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@#Objective To observe the effects of fastigial nucleus stimulation(FNS)combined with rehabilitation on vascular dementia.Methods63 vascular dementia patients were randomly divided into FNS group(40 patients)and control group(23 patients).Patients in the FNS group were treated with FNS and rehabilitation therapy,while those in the control group were treated with rehabilitation therapy only.Cognitive function were evaluated with Mini-Mental State Examination(MMSE),activities of daily living(ADL)were evaluated with Barthel Index(BI),cerebral blood flow velocity before and after therapy was detected with transcranial Doppler(TCD).ResultsThe scales of MMSE and BI increased significantly;the clinical efficiency was 95%.Cerebral blood flow velocity after therapy improved significantly(P<0.01).ConclusionFNS can improve the cognitive function and ADL in vascular dementia patients,that may be related with the improvement of cerebral blood flow.

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Objective:To establish rat models with Alzheimer's disease(AD)induced by ?-Amyloid1-40,and to observe the effects of Fastigial nucleus stimulation(FNS)on spatial memory and learning ability and the expression of bcl-2 and Bax of hippocampus area in the rats.Methods:A?1-40 was microinjected into CA1 subfield in the right hippocampus of rats.Cerebellar dentate nucleus and fastigial nucleus had been stimulated separately before the model was made.The spatial memory and learing ability of the rats were evaluated by the Morris water maze procedure in 28 days after the injection.The expression of bcl-2 and Bax were determined by immunohistochemistry method.Results:The escape latency of the place navigation in the AD group was singnificiantly longer than the sham injection group(P

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Objective To investigate the effects of cerebellum fastigial nucleus stimulation (FNS) on right middle cerebral artery occlusion (MCAO) rats with autonomic cardiovascular function disturbances. Methods MCAO model was employed in this study. A total of 60 MCAO rats were randomly divided into FNS group and non cerebellum fastigial nucleus stimulation group (NFNS). The time domain, power spectral components, and chaos of heart rate variability (HRV) were analyzed. Results The power spectral components and chaos of HRV at 3, 5, and 10 d after MCAO were significantly lower than those in the sham group ( P

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Objective To observe the effects of electrical stimulation of the cerebellum′s fastigial nucleus on neurogenic autonomic functional disturbances in rats after ischemic stroke. Methods Right middle cerebral artery occlusions (MCAOs) were performed on rats and their heart rate variability (HRV) was analysed. The MCAO rats were randomly divided into a group whose cerebellar fastigial nuclei (FNS) were stimulated and a control group. The power spectrum components and chaos of their heart rate variability were analysed. The MCAOs were performed after two cerebellar fastigial nuclei had been destroyed by pretreatment with ibotenic acid (IBO), to investigate the effect of stimulating the cerebellum′s fastigial nucleus on heart rate variability. Results The power spectral components and chaos in the heart rate variability of the MCAO rats were reduced, and there was a significant difference in the effectiveness rate compared with the sham groups (P

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Objective:To investigate the effects of fastigial nucleus stimulation(FNS)by using Cerebrovascular Functional Therapy(CVFT)on Cerebrovascular Activity(CVA)parameters and blood pressure,plasma glucose,and plasma lipid.Methods:By using CVFT,60 high risk persons received the special intervention therapy of FNS.CVA was measured 1 month,2 months,3 months,6 months before and after FNS and blood pressure,plasma glucose and plasma lipid are examined 6 months before after FNS.Results:Through intervention therapy,research objects had improved in CVA(P

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Electrical stimulation of the cerebellar fastigial nucleus(FN) increases cerebral blood flow(CBF) and reduces brain damage after focal cerebral ischemia. The authors studied whether the neuroprotection elicited from electrical stimulation of the cerebellar FN is attibutable to the elevation in regional CBF(rCBF) or reduction in release of excitatory amino acid sprague-Dawley rats were anesthtized with a mixture of halothane(3% for the indurction and 1% for maintenance) and oxygen and artificially ventilated through a tracheal cannula. Arterial pressure, blood gases and body temperature were monitored. The middle cerebral artery(MCA) was occluded distal to the lenticulostriate branches. The FN was then for 2 hours, over the regions corresponding to the ischemic core and penumbra. Postiischemic release of glutamate and aspartate were measured by microdialysis for 2 hours at the same site of measurement of rCBF. Infarct volume was determined 8 hours later in 2,3,5-triphenyl tetrazolium chloride(TTC)-stained sections FN stimulation(n=12) increased mean arterial pressure by 28+/-16mmHg. In nonstimulated control rats(n=12), mean AP was not changed significantly during the experimental procedures. Compared with nonstimulated animal, stimulation of FN for 1 hour following MCA occlusion siginficantly increased rCBF in ischemic core and penumbra by 53.6% and 67.6% respectively. And the volume of infarction decreased by 42% at 8 hours after MCA occlusion. The concentration of glutamate and aspartate in ischemic core after MCA occlusion increased both in the control group(to 12.2+/-3.3 folds and 10.4+/-4.1 folds respectively) and in the stimulation group(10.5+/-2.8 and 11.2+/-4.1 folds, respectively). The concentration of glutamate and aspartate in penumbra did change significantly neither in the control group(to 2.5+/-1.3 folds and 1.8+/-0.6 folds respectively) nor in the stimulation group(1.9+/-0.5 folds and 2.1+/-0.4 folds, respectively). There was no significant difference between the two groups.

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Animales , Ratas , Presión Arterial , Ácido Aspártico , Temperatura Corporal , Encéfalo , Isquemia Encefálica , Catéteres , Estimulación Eléctrica , Aminoácidos Excitadores , Gases , Ácido Glutámico , Infarto , Microdiálisis , Oxígeno , Ratas Sprague-Dawley

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Objective To design an electrostimulator for cerebellar fastigial nucleus stimulus, which is controlled with singlechip system and using EEG(Electroencephalogram)to modulate amplitude of the carrier wave. Methods The EEG with instrumentation amplifier of high CMRR (Common Mode Rejection Ratio) and some filters are collected. The electric insulation is achieved by using linear optocouplers on the parts of input and output. Results The stimulator can solve the problem of adaptability for wave to simulate the body, and is safe, non -invasive, and of obvious therapy for ischemic cerebrovascular disease. Conclusion The cerebellar fastigial nucleus stimulus can cure ischemic cerebrovascular disease obviously, and the modulation with EEG can solve the problem of adaptability for wave to simulate the body.