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BACKGROUND: Apathy is a multidimensional syndrome referring to a primary lack of motivation, frequent in survivors of stroke. And prior studies have demonstrated the negative effect of apathy on recovery from stroke. METHODS: A randomized controlled study of acute stroke patients. Four hundred and eighty-eight patients without evidence of apathy or depression at the initial visit were consecutively recruited, 258 males and 230 female. Patients were block randomized into 2 groups. Group A (nâ¯=â¯245) and Group B (nâ¯=â¯243) had physiotherapy according to Motor Relearning Program and Bobath in the first 4 weeks, respectively. The supplemental treatment did not differ in the 2 groups. Patients were assessed with Apathy Evaluation Scale-Clinical, National Institutes of Health Stroke Scale scores, Barthel Index scores, Mini-Mental State Examination scores, Hamilton Depression Scale scores, and Hamilton Anxiety Scale scores upon admission. At 1-, 3-, 6-, 9-, and 12-month follow-up after stroke, patients were assessed for diagnosis and severity of apathy using the Apathy Evaluation Scale-Clinical. RESULTS: Baseline characteristics of the subjects are age mean 65.1 (standard deviations, SD 10.9); 47.1% female; Apathy Evaluation Scale-Clinical mean 24.9 (SD 4.7); National Institutes of Health Stroke Scale mean 3.9 (SD 3.8); Barthel Index mean 87.9 (SD 8.7); Mini-Mental State Examination mean 23.3 (SD 4.5); Hamilton Depression Scale mean 17.5 (SD 6.6); and Hamilton Anxiety Scale mean 14.4 (SD 6.2). Participants in both groups had similar levels of apathy symptoms at study admission (Motor Relearning Program, meanâ¯=â¯24.78, SDâ¯=â¯4.62; Bobath, meanâ¯=â¯25.07, SDâ¯=â¯4.75). The Apathy Evaluation Scale scores of participants in both groups demonstrated to decline gradually from month 1 to month 12. Motor Learning Program participants had significantly less apathy severity compared with Bobath participants with respect to each time point. Participants given Bobath approach were 1.629 times more likely to develop poststroke apathy than patients given Motor Relearning Program over 12 months. CONCLUSIONS: Physiotherapy treatment in acute stroke rehabilitation using Motor Relearning program was significantly more effective in preventing of new onset of apathy following stroke compared with Bobath approach.
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Apatia , Depressão/prevenção & controle , Aprendizagem , Destreza Motora , Modalidades de Fisioterapia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Atividades Cotidianas , Idoso , China , Depressão/diagnóstico , Depressão/fisiopatologia , Depressão/psicologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca2+/CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.
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Sinalização do Cálcio/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ácido Salicílico/efeitos adversos , Zumbido/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Ratos , Ratos Wistar , Ácido Salicílico/farmacologia , Zumbido/induzido quimicamente , Zumbido/patologiaRESUMO
BACKGROUND: Apathy is a multidimensional syndrome referring to a primary lack of motivation that occurs frequently in survivors of stroke. Higher C-reactive protein (CRP) level was associated with higher apathy scores among Alzheimer disease cases. However, data on the relationship between CRP levels and apathy in patients with stroke are lacking. So, we hypothesized an association between CRP and poststroke apathy (PSA). METHODS: Two hundred ninety-two consecutive patients with stroke were recruited within 7 days after stroke. Apathy symptoms were assessed at baseline and at 1, 3, and 6 months after stoke using the Apathy Evaluation Scale-Clinical (AES-C). Demographic and clinical information were obtained using the National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, Mini-Mental State Examination (MMSE) scores, Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores. CRP was measured at baseline. The presence and the location of infarcts were evaluated using magnetic resonance imaging. RESULTS: Apathy at baseline was significantly associated with body mass index (BMI), NIHSS, BI, MMSE, HAMD, and CRP (P < .05) upon admission. PSA at 6 months was significantly associated with elevated CRP concentrations, high AES-C score, and low BI score (P < .05) upon admission. The AES-C scores peaked 3 months after stroke, but then abated over 6 months. CONCLUSIONS: CRP, BMI, MMSE, depression, and disability are closely related to apathy during the acute stage of ischemic stroke. Lower BI scores, higher CRP concentrations, and apathy in acute stroke phase increased the risk of PSA at 6 months.
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Apatia , Isquemia Encefálica/sangue , Isquemia Encefálica/psicologia , Proteína C-Reativa/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Escalas de Graduação Psiquiátrica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
OBJECTIVE: To determine the appropriate treatments for post-ischaemic stroke depression at different times after stroke. DESIGN: A single-blind, randomized, controlled trial that compared three intervention groups, with subgroups stratified by time after stroke. SETTING: Outpatient clinic. SUBJECTS: Eligible patients were recruited at discharge ( n = 73) and three ( n = 67), six ( n = 65), and nine months ( n = 69) after discharge, and patients completed mood questionnaires. INTERVENTIONS: Patients were randomly distributed into three groups: Group A received placebos and participated in general discussions; Group B, received citalopram and participated in general discussions; and Group C, received placebos and underwent cognitive behavioural therapy. All three groups participated in rehabilitation during three months of follow-up. MAIN MEASURES: Outcome was assessed three months after baseline using the 17-item Hamilton Depression Scale (HAMD17) and the Bech-Rafaelsen Melancholia Scale (MES). During treatment, the Udvalg for Kliniske Undersogelser side-effect scale was also administered. RESULTS: When stratification was not considered, the scores of Group B on the Melancholia Scale were lower than those of Group A ( P = 0.02); when the four time-based subgroups were analysed, significant differences were observed between Groups A and B (PMES = 0.02, PHAMD17 = 0.02) in the group recruited six months after discharge and between Groups A and C (PMES = 0.01) in the last time period nine months after discharge. CONCLUSIONS: The effects of citalopram or cognitive behavioural therapy is similar to the effect of rehabilitation alone for early-onset post-ischaemic depression; rehabilitation and citalopram for delayed-onset post-ischaemic depression; and rehabilitation and cognitive behavioural therapy for late-onset post-ischaemic depression are more effective than rehabilitation alone.
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Isquemia Encefálica/psicologia , Transtorno Depressivo/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/psicologia , Idoso , Antidepressivos de Segunda Geração/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/reabilitação , Citalopram/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia , Método Simples-Cego , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Depressive symptoms are commonly observed in Alzheimer's disease (AD). The underlying mechanisms of depressive symptoms in AD remain unclear; frontolimbic circuitry dysfunction may play a role. We aimed to investigate the microstructural integrity of frontolimbic connectivity of specific fiber tracts in AD patients with and without depressive symptoms using diffusion tensor imaging (DTI). METHODS: Eleven AD patients with depressive symptoms (dep-AD), 18 AD patients without depressive symptoms (nondep-AD), and 18 normal control (NC) subjects were included. The cingulum bundle (CB), uncinate fasciculus (UF), and fornix, mainly frontolimbic connectivity, were measured by DTI tractography and the metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were calculated. RESULTS: Compared with NC subjects, both dep-AD and nondep-AD patients showed significant differences for all indices in the fornix and significantly decreased FA and increased MD and RD in the bilateral CB and UF. When compared to nondep-AD patients, dep-AD patients showed significantly increased MD and RD in the bilateral CB and right UF. CONCLUSION: Depressive symptoms in AD patients may be involved in greater microstructural abnormalities of frontolimbic connectivity and myelin injury in the bilateral CB and right UF might contribute to the pathophysiology of depressive symptoms in AD.
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Doença de Alzheimer , Depressão , Lobo Frontal , Sistema Límbico , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Conectoma/métodos , Depressão/diagnóstico , Depressão/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , MasculinoRESUMO
BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.
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Doenças de Pequenos Vasos Cerebrais , Leucócitos , Análise da Randomização Mendeliana , Telomerase , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças de Pequenos Vasos Cerebrais/genética , China , População do Leste Asiático/genética , Predisposição Genética para Doença , Genótipo , Leucócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Telomerase/genética , Telômero/genéticaRESUMO
Atherosclerosis is an important pathophysiological basis of atherothrombotic stroke (ATS), and inflammation plays a significant role in atherosclerosis formation. In this study, single-nucleotide polymorphisms (SNPs) in three key inflammation-related genes, 5-lipoxygenase activating protein (ALOX5AP), phosphodiesterase 4D (PDE4D), and interleukin-1α (IL-1α), were investigated to determine their association with ATS in Northern Han Chinese. Six-hundred and eighty-two ATS patients and 598 unrelated controls were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and matrix-assisted laser desorption ionization time-of-flight mass spectrometry primer extension. The genotype and allele frequencies of each SNP were statistically analyzed. Risk of ATS was found for the ALOX5AP SG13S114A/T AA genotype (P = 0.040) and A allele (P = 0.033), PDE4D SNP83C/T TT genotype (P = 0.010) and T allele (P = 0.008) and SNP219A/G GG genotype (P = 0.025) and G allele (P = 0.022), and the IL-1α-889C/T T allele (P = 0.035). The differences still remained significant after adjustment. The ALOX5AP HapA haplotype was not correlated with ATS (P = 0.834), but GCGA represented an at-risk haplotype (P = 0.008). Furthermore, the PDE4D AA haplotype at SNP219-220 might be an at-risk haplotype (P = 0.013), while GA might be a protective haplotype (P = 0.005). The ALOX5AP (SG13S114A/T), PDE4D (SNP83C/T, 219A/G), and IL-1α (-889C/T) SNPs were associated with an increased risk of ATS in Northern Han Chinese.
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Proteínas Ativadoras de 5-Lipoxigenase/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Predisposição Genética para Doença/genética , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Alelos , Povo Asiático/genética , Aterosclerose/complicações , Isquemia Encefálica/complicações , China , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Inflamação/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Trombose/complicaçõesRESUMO
Central nervous system (CNS) disorders, such as ischemic stroke, neurodegenerative diseases, multiple sclerosis, traumatic brain injury, and corresponding neuropathological changes, often lead to death or long-term disability. Long non-coding RNA (lncRNA) is a class of non-coding RNA with a transcription length over 200 nt and transcriptional regulation. lncRNA is extensively involved in physiological and pathological processes through epigenetic, transcription, and post-transcriptional regulation. Further, dysregulated lncRNA is closely related to the occurrence and development of human diseases, including CNS disorders. HOX Transcript antisense RNA (HOTAIR) is the first discovered lncRNA with trans-transcriptional regulation. Recent studies have shown that HOTAIR may participate in the regulation of the occurrence and development of CNS disorders. In addition, HOTAIR has the potential to become a new biomarker for the diagnosis and prognosis assessment of CNS disorders and even provide a new therapeutic target for CNS disorders. Here, we reviewed the research results of HOTAIR in CNS disorders to provide new insights into the pathogenesis, diagnostic value, and therapeutic target potential of HOTAIR in human CNS disorders.
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Analyzing and understanding human actions in long-range videos has promising applications, such as video surveillance, automatic driving, and efficient human-computer interaction. Most researches focus on short-range videos that predict a single action in an ongoing video or forecast an action several seconds earlier before it occurs. In this work, a novel method is proposed to forecast a series of actions and their durations after observing a partial video. This method extracts features from both frame sequences and label sequences. A retentive memory module is introduced to richly extract features at salient time steps and pivotal channels. Extensive experiments are conducted on the Breakfast data set and 50 Salads data set. Compared to the state-of-the-art methods, the method achieves comparable performance in most cases.
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Memória de Curto Prazo , Redes Neurais de Computação , Atividades Humanas , Humanos , Memória de Longo Prazo , RiosRESUMO
Epilepsy is the result of a group of transient abnormalities in brain function caused by an abnormal, highly synchronized discharge of brain neurons. MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules that participate in a series of important biological processes. Recent studies demonstrated that miRNAs are involved in a variety of central nervous system diseases, including epilepsy. Although the exact mechanism underlying the role of miRNAs in epilepsy pathogenesis is still unclear, these miRNAs may be involved in the inflammatory response in the nervous system, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, glial cell proliferation, epileptic circuit formation, impairment of neurotransmitter and receptor function, and other processes. Here, we discuss miRNA metabolism and the roles of miRNA in epilepsy pathogenesis and evaluate miRNA as a potential new biomarker for the diagnosis of epilepsy, which enhances our understanding of disease processes.
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Neurological disorders are mainly characterized by progressive neuron loss and neurological deterioration, which cause human disability and death. However, many types of neurological disorders have similar pathological mechanisms, including the neuroinflammatory response. Various microRNAs (miRs), such as miR-21, miR-124, miR-146a, and miR-132 were recently shown to affect a broad spectrum of biological functions in the central nervous system (CNS). Microglia are innate immune cells with important roles in the physiological and pathological activities of the CNS. Recently, abnormal expression of miR-124 was shown to be associated with the occurrence and development of various diseases in CNS via regulating microglia function. In addition, miR-124 is a promising biomarker and therapeutic target. Studies on the role of miR-124 in regulating microglia function involved in pathogenesis of neurological disorders at different stages will provide new ideas for the use of miR-124 as a therapeutic target for different CNS diseases.
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Previous studies have suggested that jumonji AT-rich interactive domain 1B (JARID1B) plays an important role in the genesis of some types of cancer, and it is therefore considered to be an important drug target protein. Although the expression of JARID1B has been researched in some types of cancer, little is known about JARID1B expression in glioma and its function in the tumorigenesis of gliomas. In the present study, we examined the expression of JARID1B in glioma. In addition, RT-PCR, western blot analysis and immunohistochemical analysis were performed using glioma tissue samples and the results revealed that JARID1B expression increased according to the histological grade of glioma. However, in the normal brain tissue samples JARID1B expression was barely detected. KaplanMeier analysis revealed that higher JARID1B expression in patients with glioma was associated with a poorer prognosis. The overexpression of JARID1B stimulated the proliferation and migration of glioma cells as well as sphere formation, whereas suppressing the expression of JARID1B produced opposite effects. The overexpression of JARID1B increased the tumorigenicity of glioma cells in vivo in a nude mouse xenograft model of glioma. Moreover, the activation of phosphorylated (p-)Smad2 contributes to JARID1B-induced oncogenic activities. These findings suggest that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese/patologia , Progressão da Doença , Glioma/genética , Glioma/patologia , Histona Desmetilases com o Domínio Jumonji/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Histona Desmetilases com o Domínio Jumonji/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Proteínas Nucleares/metabolismo , Fosforilação/efeitos dos fármacos , Pirazóis/farmacologia , Pirróis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo , Proteína Smad2/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologiaRESUMO
Following the publication of the article, the authors noted that there were certain errors in the data and presentation of some of the parts of the figures. The correct images are shown below. [the original article was published in the International Journal of Molecular Medicine 38: 172-182, 2016; DOI: 10.3892/ijmm.2016.2614].
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Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RTPCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity.
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Encéfalo/metabolismo , Epilepsia/genética , Epilepsia/patologia , Regulação da Expressão Gênica/genética , Neuropeptídeo Y/metabolismo , Somatostatina/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Mutação/genética , Neuropeptídeo Y/genética , Canais de Potássio/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Mutantes , Ratos Wistar , Somatostatina/genética , Tremor/genética , Tremor/fisiopatologiaRESUMO
Cerebral infarct (CI) is a common disease of older adults, which increases the risk for cognitive impairment or dementia. CI-associated mild cognitive impairment is a potential prodromal stage of serious cognitive impairment. The grand total EEG (GTE) score is a rating scale for clinical electroencephalography (EEG) analyses, which is useful in the evaluation of different types of cognitive impairment. Sixty-five patients with CI underwent neuropsychological testing and resting state EEG. Spearman rank correlation analysis was used to investigate the relationship between a short version of the GTE score and severity of cognitive impairment in CI. Significant correlations with deteriorating cognition (combined Montreal Cognitive Assessment/clock drawing test) were found for the overall short GTE score (Spearman rank correlation, p = -0.61, r = -0.88491, P = 0.009) and for the subscore "Frequency of Rhythmic Background Activity" (p = -0.63, r = -0.92559, P = 0.007). In conclusion, the GTE short score and Frequency of Rhythmic Background Activity were increased with the deteriorating cognitive impairment in patients with CI.
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Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Eletroencefalografia/métodos , Processamento de Sinais Assistido por Computador , Potenciais de Ação/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Psicometria , Sensibilidade e Especificidade , Estatística como Assunto , Estatísticas não ParamétricasRESUMO
The midbrain periaqueductal gray (PAG) is a substantial component of the descending modulatory network to control on nociceptive transmission and autonomic functions. Also, accumulated evidence has suggested that the PAG plays a crucial role in regulating migraine headache, a neurovascular disorder. The purpose of this study was to employ ELISA methods to examine the levels of prostaglandin E2 (PGE2) and calcitonin-gene related peptide (CGRP) in the PAG of rats who received ovariectomy and subsequent hormone replacement with 17ß-estradiol, progesterone, or the combination of 17ß-estradiol and progesterone. In addition, using Western blot analysis we examined expression of subtypes of PGE2 receptor in the PAG of rats with different conditions of female sex hormones. Results of our study demonstrated that lack of female sex hormones significantly increased the levels of PGE2 and CGRP in the dorsolateral PAG (P < 0.05) as well as expression of PGE2 EP3 receptors (P < 0.05). Furthermore, a liner relationship was observed between PGE2 and CGRP in the PAG (r = 092, P < 0.01). Also, inhibiting EP3 receptors by chronic administration of L-798106 (EP3 antagonist) into the lateral ventricles significantly attenuated expression of CGRP in the PAG of ovariectomized animals (P < 0.05 vs. vehicle control). Overall, our findings for the first time show that (1) circulating 17ß-estradiol and/or progesterone influences the levels of PGE2 and CGRP in the PAG; (2) a lower level of 17ß-estradiol and/or progesterone augments PGE2 and its EP3 receptor; and (3) PGE2 plays a role in regulating expression of CGRP in the PAG.
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Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dinoprostona/metabolismo , Hormônios Esteroides Gonadais/deficiência , Substância Cinzenta Periaquedutal/metabolismo , Administração Cutânea , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ovariectomia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Progesterona/farmacologia , Progestinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina E/metabolismoRESUMO
OBJECTIVE: We carried out a meta-analysis focusing on the relationships between rs1137070 C>T and rs1799836 A>G polymorphisms in the MAO gene as a modifier of Parkinson disease (PD) susceptibility. METHOD: A literature search of the Cochrane Library Database, Web of Science, PubMed, CINAHL, EMBASE, and the Chinese Biomedical Database (CBM) was performed without any language restrictions on articles published before April 10st, 2014. We choose the STATA 12.0 statistical software to deal with statistical data. Crude odds ratios (ORs) estimates with 95% confidence interval (95% CI) were also provided. RESULTS: Fourteen independent case-control studies met our predetermined inclusion criteria and were included in the meta-analysis. Two major polymorphisms rs1137070 C>T and rs1799836 A>G in the MAO gene were performed in this meta-analysis. When all the eligible studies were pooled into the meta-analysis, our results indicated that rs1137070 C>T polymorphism and rs1799836 A>G polymorphism have statistically significant correlation with the increased risk of PD in the majority groups. Ethnicity-stratified analysis revealed a relation between the rs1137070 C>T polymorphism and PD risk among Asians and Caucasians in the majority groups. Additionally, there was an apparent association between the rs1799836 A>G variant and PD risk among the Asian populations under 4 genetic models (G allele vs. A allele: OR=0.84, 95% CI=0.72-0.97, P=0.021; GG vs. AA+AG: OR=1.73, 95% CI=1.25-2.39, P=0.001; GG vs. AA: OR=1.56, 95% CI=1.18-2.04, P=0.002; GG vs. AG: OR=3.42, 95% CI=1.86-6.30, P<0.001; respectively). CONCLUSION: The relationships in the polymorphisms of rs1137070 C>T and rs1799836 A>G in the MAO gene with PD susceptibility observed in our meta-analyses support the view that the MAO gene may play an important role in the development of PD.
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Predisposição Genética para Doença/genética , Monoaminoxidase/genética , Doença de Parkinson/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Estudos de Associação Genética , Humanos , Masculino , Razão de ChancesRESUMO
Aluminum-induced neuronal injury has been implicated in various neurodegenerative disorders. However, the underlying mechanism involved in this pathogenesis still remains unknown. Our present findings demonstrated that chronic aluminum exposure resulted in spatial learning impairment and significantly increased intracellular calcium level in the hippocampus of rats. Examination of the associated protein molecules essential for induction and maintenance of long-term potentiation revealed that aluminum exposure could increase the expression level of calmodulin (CaM), but the expression levels of CaM-dependent protein kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (CREB) were significantly reduced, whereas the total protein levels of CaMKII and CREB did not change in the aluminum-treated hippocampus. Thus, we provide a previously unrecognized mechanism whereby chronic aluminum exposure impairs hippocampal learning and memory, at least in part, through disruption of intracellular calcium homeostasis and CaM/CaMKII/CREB signaling pathway.
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Alumínio/toxicidade , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Homeostase/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Alumínio/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Transtornos da Memória/fisiopatologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The heartwood of Caesalpinia sappan L. (Leguminosae), a widely used Chinese medicine in folk, has been used for the treatment of traumatic injury, stasis pain, amenorrhea, dysmenorrheal, as well as stabbing pain in the chest, abdomen and so on. Protosappanin B and brazilin, as the major bioactive homoisoflavones of Sappan Lignum, are used as the marker components for the quality control of the herb in China Pharmacopoeia. AIM OF THE STUDY: To establish a sensitive LC/MS/MS method for investigating the pharmacokinetic properties of protosappanin B and brazilin in rats after oral administration of Sappan Lignum extract, and compare their pharmacokinetics difference between normal and streptozotocin-treated rats. MATERIAL AND METHODS: A rapid, selective and sensitive LC/MS/MS method was developed and validated for the simultaneous quantification of protosappanin B and brazilin in rat plasma. Normal and streptozotocin-treated rats were orally administered with the Sappan Lignum extract at the same dose of 2.83 g extract/kg body weight (equivalent to 35.56 mg/kg of protosappanin B and 52.25 mg/kg of brazilin), respectively. RESULTS: After oral administration of Sappan Lignum extract, a remarkable increase (p<0.05) in the value of AUC0-24h, AUC0-∞, Cmax and T1/2 associated with protosappanin B and brazilin was observed in the streptozotocin-treated group. Compared with the normal rats, elimination of both compounds in the streptozotocin-treated rats was slower. CONCLUSION: The established method was successfully applied to compare the pharmacokinetic behaviors of protosappanin B and brazilin in rat plasma after oral administration of Sappan Lignum extract between normal and streptozotocin-treated groups; the results might suggest the accumulation of both compounds in diabetic pathologic states and the adverse reaction should be considered when it was used.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/farmacocinética , Isoflavonas/farmacologia , Isoflavonas/farmacocinética , Animais , Área Sob a Curva , Benzopiranos/química , Benzopiranos/farmacocinética , Benzopiranos/farmacologia , Caesalpinia/química , Cromatografia Líquida/métodos , Diabetes Mellitus Experimental/sangue , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Fabaceae/metabolismo , Hipoglicemiantes/química , Isoflavonas/química , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem/métodosRESUMO
OBJECTIVE: To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer's disease (AD). METHODS: The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 microL (10 microg/microL) amyloid-beta peptide 1-40(Abeta1-40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. RESULTS: The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P< 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P< 0.01). CONCLUSION: ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.