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1.
Braz J Med Biol Res ; 52(9): e8533, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483000

RESUMO

This study aimed to evaluate the effect of a newly designed intensive caregiver education program (ICEP) on reducing cognitive impairment, anxiety, and depression in acute ischemic stroke (AIS) patients. One hundred and ninety-six AIS patients were divided into ICEP group and Control group in a 1:1 ratio using blocked randomization method. In the ICEP group, the caregivers received ICEP, while in the Control group caregivers received usual education and guidance. All patients received conventional rehabilitation treatment. Cognitive impairment (assessed by Mini Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score), anxiety (assessed by Hospital Anxiety and Depression Scale (HADS)-A score and Self-rating Anxiety Scale (SAS) score), and depression (assessed by HADS-D score and Self-rating Depression Scale (SDS) score) were assessed at baseline (M0), 3 months (M3), 6 months (M6), and 12 months (M12). Cognitive impairment score at M12 and cognitive impairment score change (M12-M0) were increased, while cognitive impairment rate at M12 was reduced in the ICEP group compared with the Control group. Anxiety score change (M12-M0), anxiety score at M12, and anxiety rate at M12 were decreased in the ICEP group compared with the Control group. Depression score change (M12-M0), depression score at M12, and depression rate at M12 were lower in the ICEP group compared with the Control group. Further subgroup analysis based on baseline features also provided similar results. In conclusion, ICEP effectively reduced cognitive impairment, anxiety, and depression in AIS patients.


Assuntos
Transtornos de Ansiedade/prevenção & controle , Ansiedade/prevenção & controle , Cuidadores , Disfunção Cognitiva/prevenção & controle , Transtorno Depressivo/prevenção & controle , Educação em Saúde/métodos , Acidente Vascular Cerebral/enfermagem , Adulto , Ansiedade/etiologia , Transtornos de Ansiedade/etiologia , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Transtorno Depressivo/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral
2.
Nervenarzt ; 90(9): 921-925, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31440769

RESUMO

BACKGROUND: In Germany, approximately 1.6 million people are currently suffering from dementia. The prevalence of the disease is expected to double by 2060. To date there is no treatment that can prevent the onset of dementia. For this reason, the development of prevention strategies for cognitive decline and dementia is crucial. OBJECTIVE: Presentation of studies on dementia prevention by treatment of arterial hypertension. Overview of current multidomain interventional studies on dementia prevention. MATERIAL AND METHODS: Narrative review. RESULTS: Whereas in three previous randomized controlled trials on antihypertensive treatment a reduction of dementia risk could not be found, the recent SPRINT-MIND study demonstrated a reduced risk of mild cognitive impairment (MCI) and in the trend for dementia by intensified hypotensive treatment. Multidomain interventional studies suggest preventive effects, particularly in specific risk groups and also highlight the challenge of adherence to lifestyle modifications. CONCLUSION: The treatment of modifiable risk factors can have a preventive effects on cognitive decline and dementia. More research is needed to identify subgroups with the greatest likelihood of benefits.


Assuntos
Anti-Hipertensivos/uso terapêutico , Disfunção Cognitiva , Demência , Hipertensão/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Demência/complicações , Demência/prevenção & controle , Alemanha , Humanos , Fatores de Risco
3.
BMC Public Health ; 19(1): 659, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142290

RESUMO

BACKGROUND: Several observational studies have shown that exercise reduces the risk of cognitive decline; however, evidences from long-term, well-conducted, randomized controlled trials are scanty. The principal aim of this study is to verify whether a long-term program of multimodal supervised exercise improves the cognitive function and/or reduces the rate of cognitive decline in older adults at different degrees of risk for dementia. METHODS/DESIGN: EPD is a parallel group, double-blind, randomized controlled trial. Community-dwelling volunteers aged 50 years or more are being recruited from different community centers and screened for eligibility. Enrolled subjects are being divided in 3 groups: a) without subjective or objective cognitive impairment, b) with subjective memory complaints, and c) with mild cognitive impairments. Participants in each group (at least 180) are being randomly assigned (1:1) to an experimental group, performing a supervised training including aerobic and resistance exercises of moderate/high intensity, or to a control group. Primary outcome will be 48-months changes in Mini Mental State Examinations. Secondary outcomes will be changes in several cognitive tests including a composite cognitive score. Time points will be at baseline, and at 6, 12, 24, 36 and 48 months. Statistical analysis will be done as intention to treat, complete case and mixed model analysis. DISCUSSION: EPD is the first trial to examine the effects of a long exercise program (48 months) on cognitive performances. If successful, this trial may provide evidence for using long-term and multimodal exercise interventions for dementia prevention programs in the aging population. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the code NCT02236416 .


Assuntos
Demência/prevenção & controle , Exercício/psicologia , Idoso , Cognição , Disfunção Cognitiva/prevenção & controle , Demência/psicologia , Método Duplo-Cego , Feminino , Humanos , Vida Independente , Masculino , Memória , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Medição de Risco
4.
Medicine (Baltimore) ; 98(18): e15383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045788

RESUMO

BACKGROUND: Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance and inflammatory factors to investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) and inflammation in patients after general anaesthesia. METHODS: Literatures were searched in several electronic databases and studies were selected by following precise inclusion criteria. We searched PubMed, EMBASE, the Cochrane Library, China Academic Journals full-text database (CNKI), and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD and inflammation in patients who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated quality of methodology against inclusion and exclusion criteria. Meta-analyses of pooled ORs of POCD incidences and mean differences in neurocognitive assessment scores and inflammation levels were carried out and subgroup analyses were performed. Stata 12.0 was used to conduct our meta-analysis. RESULTS: Twenty-six RCTs were included. Compared with controls, perioperative dexmedetomidine treatment significantly reduced the incidence of POCD (pooled ORs = 0.59, 95% confidence interval (CI) 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (standardized mean difference (SMD) = 1.74, 95% CI 0.43-3.05) on the first postoperative day. Furthermore, perioperative dexmedetomidine treatment significantly decreased IL-6 (SMD = -1.31, 95% CI -1.87-0.75, P < .001) and TNF-α (SMD = -2.14, 95% CI -3.14-1.14, P < .001) compared to saline/comparators treatment. In the stratified analysis by surgical type, age, type of control, and study region, the differences were also significant between dexmedetomidine- and saline-treated patients. CONCLUSION: Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia Geral/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/administração & dosagem , China , Humanos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Testes de Estado Mental e Demência , Razão de Chances , Período Perioperatório , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/biossíntese
5.
Curr Med Sci ; 39(2): 196-203, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016510

RESUMO

With the intensification of the aging process of the world, Alzheimer's disease (AD), which is the main type of senile dementia, has become a primary problem in the present society. Lots of strategies have been used to prevent and treat AD in animal models and clinical trials, but most of them ended in failure. Panax notoginseng saponins (PNS) contain a variety of monomer compositions which have been separated and identified. Among of the monomer compositions, notoginseng saponin Rg1 (Rg1) accounts for 20% of the cultivation of panax notoginseng roots. And now PNS have been reported to be widely used to treat cardio-cerebrovascular diseases and have neuroprotective effects to restrain the ß-amyloid peptide (Aß)25-35-mediated apoptosis. Moreover, it is reported that PNS could accelerate the growth of nerve cells, increase the length of axons and promote synaptic plasticity. Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated. To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism, we established the cognitive impairment model in rats through Aß1-42 (2.6 µg/µL, 5 µL) injection and then treated the rats with Rg1 (25, 50 and 100 mg/kg) administered intragastrically for 4 weeks. We observed that Aß1-42 could induce spatial learning and memory deficits in rats. Simultaneously, Aß1-42 injection also resulted in the reduced neuron number in cornuammonis 1 (CA1) and dentate gyrus (DG) of hippocampus, as well as the increased level of hyperphosphorylated ß-amyloid precursor protein (APP) at Thr668 site with up-regulation of ß-APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) and down-regulation of a disintegrin and metalloprotease domain-containing protein 10 (ADAM10) and insulin-degrading enzyme (IDE). Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss, and inhibited the ß-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression, and increasing the expression of ADAM10 and IDE. We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability, which might be a viable candidate in AD therapy probably through reducing the generation of Aß and increasing the degradation of Aß.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Disfunção Cognitiva/prevenção & controle , Panax notoginseng/química , Fragmentos de Peptídeos/metabolismo , Saponinas/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Disfunção Cognitiva/metabolismo , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Presenilina-1/metabolismo , Ratos , Ratos Sprague-Dawley
6.
Life Sci ; 226: 202-209, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991061

RESUMO

INTRODUCTION: Ischemic stroke is one of the leading causes of death worldwide, and extensive efforts have focused on the neuroprotective strategies to minimize complications due to ischemia. This study aimed to examine neuroprotective potential of chrysin, as a natural potent antioxidative and anti-inflammatory agent in an animal model of bilateral common carotid artery occlusion and reperfusion (BCCAO/R). METHODS: Adult male Wistar rats (250-300 g) were randomly divided into 6 groups and submitted to either sham surgery or BCCAO/R after pretreatment with chrysin (10, 30 and 100 mg/kg, once daily, for 21 consecutive days) or saline containing %5 DMSO. To make the animal model of BCCAO/R, bilateral common carotid arteries were occluded for 20 min, followed by reperfusion. Subsequently, spatial cognitive performance was evaluated in a Morris water maze (MWM), hippocampal long-term potentiation (LTP) was recorded from hippocampal dentate gyrus region, after then the hippocampal tissue content of IL-1ß and TNF-α were assayed using ELISA kits. RESULTS: The results showed that pretreatment with chrysin significantly prevented BCCAO/R-induced cognitive and hippocampal LTP impairments (p < 0.001). Additionally, BCCAO/R- induced elevation in hippocampal content of IL-1ß and TNF-α significantly (p < 0.01, p < 0.01 respectively) while pre-treatment with chrysin restored them (p < 0.01). CONCLUSION: Our data confirm that chrysin could prevent brain inflammation and thereby prevents cognitive and LTP impairments due to cerebral ischemia. So it could be a promising neuroprotective agent against cerebrovascular insufficiency states.


Assuntos
Disfunção Cognitiva/prevenção & controle , Flavonoides/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes , Isquemia Encefálica/complicações , Artérias Carótidas , Artéria Carótida Primitiva , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Encefalite/tratamento farmacológico , Encefalite/prevenção & controle , Flavonoides/uso terapêutico , Hipocampo/efeitos dos fármacos , Inflamação , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Fármacos Neuroprotetores , Estresse Oxidativo , Ratos , Ratos Wistar
7.
J Food Sci ; 84(5): 1012-1022, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31017668

RESUMO

Dietary phenolics are known for their potent antioxidant and anti-inflammatory activities, making them promising candidates for protection against neuroinflammation and neurodegeneration. Hydroalcohol extract of Egyptian species of Corchorus olitorius L. (Co) leaves was investigated for its neuroprotective effects in a lipopolysaccharide-induced neuroinflammatory mouse model. Twenty five metabolites were characterized from the bioactive extract using high-performance liquid chromatography HPLC/PDA/HRESI/MSn , revealing 1,5-dicaffeoylquinic acid (Co11) as one of the major constituents (5.7%), which was isolated and its identity was confirmed by spectral data as first report. Co significantly protected microglia against H2 O2 -induced cytotoxicity and immunohistochemistry showed reduced expression of the astrocytic marker, glial fibrillary acidic protein, and the inflammatory marker, cyclooxygenase-2. These findings correlated with significant improvement of cognitive functions and reduction of LPS-induced neurodegeneration in Co-treated mice as revealed by histopathology. The current study shows promising effects of Co in limiting neurodegeneration and cognitive impairment caused by neuroinflammation and glial cell activation. PRACTICAL APPLICATION: Information presented here shed light on the promising effects of Corchorus olitorius (Co) for the modulation of neuroinflammatory pathways improving the neuroinflammation-related neurodegeneration and cognitive decline. This makes Co a promising candidate as a nutraceutical supplement to be used against neuroinflammation-related disorders.


Assuntos
Disfunção Cognitiva/prevenção & controle , Corchorus/química , Dieta , Microglia/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Fenóis/uso terapêutico , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cromatografia Líquida de Alta Pressão , Cinamatos/análise , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Egito , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Microglia/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Fenóis/análise , Fenóis/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química
8.
Nat Neurosci ; 22(5): 820-827, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962628

RESUMO

Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline-working-memory deficits-emerges from disconnected local and long-range circuits instantiated by theta-gamma phase-amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60-76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender-receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.


Assuntos
Envelhecimento/psicologia , Envelhecimento Cognitivo , Sincronização Cortical , Lobo Frontal/fisiologia , Ritmo Gama , Memória de Curto Prazo/fisiologia , Lobo Temporal/fisiologia , Ritmo Teta , Idoso , Disfunção Cognitiva/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Estimulação Transcraniana por Corrente Contínua
9.
Lipids Health Dis ; 18(1): 100, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992016

RESUMO

Growing evidence suggests that ethanolamine plasmalogens (PlsEtns), a subtype of phospholipids, have a close association with Alzheimer's disease (AD). Decreased levels of PlsEtns have been commonly found in AD patients, and were correlated with cognition deficit and severity of disease. Limited studies showed positive therapeutic outcomes with plasmalogens interventions in AD subjects and in rodents. The potential mechanisms underlying the beneficial effects of PlsEtns on AD may be related to the reduction of γ-secretase activity, an enzyme that catalyzes the synthesis of ß-amyloid (Aß), a hallmark of AD. Emerging in vitro evidence also showed that PlsEtns prevented neuronal cell death by enhancing phosphorylation of AKT and ERK signaling through the activation of orphan G-protein coupled receptor (GPCR) proteins. In addition, PlsEtns have been found to suppress the death of primary mouse hippocampal neuronal cells through the inhibition of caspase-9 and caspase-3 cleavages. Further in-depth investigations are required to determine the signature molecular species of PlsEtns associated with AD, hence their potential role as biomarkers. Clinical intervention with plasmalogens is still in its infancy but may have the potential to be explored for a novel therapeutic approach to correct AD pathology and neural function.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Peptídeos beta-Amiloides/antagonistas & inibidores , Disfunção Cognitiva/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Plasmalogênios/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/biossíntese , Peptídeos beta-Amiloides/genética , Animais , Biomarcadores/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Plasmalogênios/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais
10.
Neurochem Res ; 44(7): 1703-1714, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30989480

RESUMO

Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in isoflurane-induced neuronal damage. Lidocaine has been demonstrated to attenuate the impairment of cognition in aged rats induced by isoflurane in our previous study. In this study, we hypothesized that lidocaine could attenuate isoflurane anesthesia-induced cognitive impairment by reducing mitochondrial damage. H4 human neuroglioma cells and 18-month-old male Fischer 344 rats were exposed to isoflurane or isoflurane plus lidocaine. Cognitive function was tested at 14 days after treatment by the Barnes Maze test in male Fischer 344 rats. Morphology was observed under electron microscope, and mitochondrial transmembrane potential, electron transfer chain (ETC) enzyme activity, complex-I-IV activity, immunofluorescence and flow cytometry of annexin V-FITC binding, TUNEL assay, and Western blot analyses were applied. Lidocaine attenuated cognitive impairment caused by isoflurane in aged Fischer 344 rat. Lidocaine was effective in reducing mitochondrial damage, mitigating the decrease in mitochondrial membrane potential (ΔΨm), reversing isoflurane-induced changes in complex activity in the mitochondrial electron transfer chain and inhibiting the apoptotic activities induced by isoflurane in H4 cells and Fischer 344 rats. Additionally, lidocaine suppressed the ratio of Bax (the apoptosis-promoting protein) to Bcl-2 (the apoptosis-inhibiting protein) caused by isoflurane in H4 cells. Lidocaine proved effective in attenuating isoflurane-induced POCD by reducing mitochondrial damage.


Assuntos
Anestésicos/uso terapêutico , Disfunção Cognitiva/prevenção & controle , Lidocaína/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Anestésicos/administração & dosagem , Anestésicos Inalatórios , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hipocampo/patologia , Humanos , Injeções Intravenosas , Isoflurano , Lidocaína/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/patologia , Doenças Mitocondriais/induzido quimicamente , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Endogâmicos F344 , Proteína X Associada a bcl-2/metabolismo
11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(3): 298-302, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30914089

RESUMO

OBJECTIVE: To investigate the characteristics of cognitive impairment in critical patients, and to explore the role of early cognitive intervention training in improving cognitive impairment in critical patients. METHODS: A prospective cohort study was conducted. 133 patients in conscious and normal intelligence admitted to intensive care unit (ICU) of Hefei Second People's Hospital from January 2015 to June 2018 were enrolled. The patients were divided into control group (n = 66) and cognitive intervention group (n = 67) according to random number table based on chronological number for entry into the study. Cognitive function was assessed by Montreal cognitive assessment scale (MoCA scale) within 24 hours after ICU admission. The patients in the cognitive intervention group received a series of scientifically designed cognitive training sessions (playing electronic musical keyboard, learning simple Spanish, clock-drawing, psychological intervention) for 2 months, and follow-up was completed if the patient was discharged from ICU. While the patients in the control group did not undertake any cognitive training. After 2 months, the cognitive function of patients in both groups were assessed with MoCA scale. Subgroup analysis was conducted according to different age groups (20-40 years old, 41-60 years old, 61-80 years old) to explore the effect of cognitive intervention training in different age groups. According to the subjective evaluation of the patient's ability to live 2 months after cognitive intervention by the patient or his relatives, receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of the total score of MoCA for patients' ability to live after cognitive intervention. RESULTS: 133 critical patients were enrolled in the final analysis. There was no significant difference in gender, age, education, complications, ICU hospitalization, sedative or analgesic drug usage between the two groups, indicating that the data of the two groups were balanced and comparable. No significant difference in MoCA scale total score or sub-item cognitive domain score within 24 hours of ICU admission was found between the two groups. After 2 months of intervention, the incidence of cognitive impairment in the cognitive intervention group was significantly lower than that in the control group [38.8% (26/67) vs. 60.6% (40/66), χ2 = 6.321, P = 0.015]. The total score of MoCA scale and four sub-item cognitive domain scores including visual space and execution power, protection of memory, attention execution, and orientation in the cognitive intervention group were significant higher than those in the control group (MoCA scale total score: 26.73±1.92 vs. 24.95±2.26, visual space and executive power score: 4.39±0.70 vs. 3.95±0.88, protection of memory score: 8.91±1.03 vs. 8.24±1.37, attention execution score: 5.21±0.77 vs. 4.79±1.00, orientation score: 5.67±0.53 vs. 5.44±0.68, all P < 0.05), but no significant difference was found in verbal skills score (2.55±0.56 vs. 2.53±0.56, P > 0.05). Subgroup analysis showed that the total MoCA scale score of the younger sample (20-40 years old, n = 20) was recovered by 2.10±1.55 in the cognitive intervention group after 2 months of cognitive intervention, which was significantly higher than that in the control group (n = 21; 0.24±2.76, P < 0.05). In the middle-aged and the older population [aged 41-60 years old (n = 20) and 61-80 years old (n = 27)], the total MoCA scale scores were recovered slightly after cognitive intervention as compared with those in the younger sample (0.43±1.47, -1.91±2.20 vs. 2.10±1.55, both P < 0.05), which were significantly lower than those in the control group [aged 41-60 years old (n = 21) and 61-80 years old (n = 24), -0.78±1.38, -4.41±2.17, both P < 0.01]. It was suggested that cognitive intervention training played an active role in the recovery of cognitive function in young critical patients. It was shown by ROC curve analysis that the area under ROC curve (AUC) of MoCA scale total score for predicting daily life ability after cognitive intervention was 0.732 with 95% confidence interval (95%CI) of 0.646-0.819. When the best cut-off value was 24.5, the sensitivity was 89.3%, the specificity was 60.2%, the positive predictive value was 85.7%, and the negative predictive value was 80.8%. CONCLUSIONS: Early cognitive intervention could efficiently abate the deterioration of cognitive function in critical patients in ICU and had significant effects on the visual space and executive power, protection of memory, attention execution and orientation. Cognitive intervention exerted significantly positive effects on the recovery of cognitive function in the younger sample population (aged 20-40 years old).


Assuntos
Terapia Cognitivo-Comportamental , Disfunção Cognitiva/prevenção & controle , Cuidados Críticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
12.
Mol Med Rep ; 19(5): 3815-3822, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896803

RESUMO

Post­operative cognitive dysfunction is a common complication after anesthesia and surgery. Sevoflurane (SEV), a widely used inhalational anesthetic, can exaggerate neuroinflammation and cause cognitive dysfunction under chronic intermittent hypoxia (CIH) conditions by downregulating hippocampal peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). In the present study, it was examined whether treatment with PPAR­Î³ agonist pioglitazone (PIO) is beneficial in counteracting SEV­induced neuroinflammation and cognitive decline in a rat model of CIH. Rats were exposed to CIH for 4 weeks. After 2 weeks of CIH, these animals underwent either 2.6% SEV or control (CON) exposure for 4 h. PIO (60 mg/kg) or vehicle (VEH) was administered orally twice daily for 2 weeks, starting one day prior to SEV or CON exposure. Compared with CIH­CON+VEH rats, CIH­SEV+VEH rats exhibited significant cognitive decline as indicated by increased latency to locate the hidden platform and shorter dwell­time in the goal quadrant in the Morris Water Maze task. Molecular studies revealed that CIH­SEV+VEH rats had increased proinflammatory cytokine expression and microglial activation in the hippocampus, which were associated with decreased PPAR­Î³ activity. Notably, SEV­induced cognitive decline and increases in proinflammatory cytokine expression and microglial activation were prevented by PIO, which increased hippocampal PPAR­Î³ activity. PIO also increased hippocampal PPAR­Î³ activity in CIH­CON rats but did not alter proinflammatory cytokine expression and microglial activation as well as cognitive function. Additionally, expression of hippocampal PPAR­α and PPAR­ß, two other PPAR isotypes, were comparable among the groups. These data suggest that PIO prevents SEV­induced exaggeration of neuroinflammation and cognitive decline under CIH conditions by upregulating hippocampal PPAR­Î³. PIO may have the potential to prevent anesthetic SEV­induced cognitive decline in surgical patients with obstructive sleep apnea.


Assuntos
Disfunção Cognitiva/prevenção & controle , Hipóxia/fisiopatologia , Inflamação/prevenção & controle , Neuroimunomodulação/efeitos dos fármacos , PPAR gama/metabolismo , Pioglitazona/farmacologia , Sevoflurano/toxicidade , Animais , Doença Crônica , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hipoglicemiantes/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Inibidores da Agregação de Plaquetas/toxicidade , Ratos , Ratos Sprague-Dawley
13.
Arch Pharm Res ; 42(5): 446-454, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900149

RESUMO

Hydrogen sulfide (H2S), a gasotransmitter molecule, has attracted attention as an endogenous signaling molecule because of its various pathological and physiological effects, including pathologies related to aging. In this review, we aimed to discuss the morphological changes in each vessel following aging, and to evaluate the possible role of H2S in the cerebrovascular alteration, such as arterial stiffness, microvessel loss, and blood-brain barrier disruption, with advancing age. Additionally, the review outlines the therapeutic efficacy of the H2S-releasing compounds on the cerebrovasculature. In the central nervous system, cerebrovascular aging can lead to the loss of blood-brain integrity, which causes cognitive impairment. The findings discussed in this review strongly support the notion that H2S has a potential therapeutic role in cerebrovascular alteration in aging.


Assuntos
Envelhecimento/fisiologia , Circulação Cerebrovascular/fisiologia , Disfunção Cognitiva/prevenção & controle , Sulfeto de Hidrogênio/metabolismo , Fármacos Neuroprotetores/farmacologia , Envelhecimento/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Microvasos/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Rigidez Vascular/efeitos dos fármacos , Rigidez Vascular/fisiologia
14.
Cochrane Database Syst Rev ; 3: CD012278, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30864746

RESUMO

BACKGROUND: Normal aging is associated with changes in cognitive function that are non-pathological and are not necessarily indicative of future neurocognitive disease. Low cognitive and brain reserve and limited cognitive stimulation are associated with increased risk of dementia. Emerging evidence now suggests that subtle cognitive changes, detectable years before criteria for mild cognitive impairment are met, may be predictive of future dementia. Important for intervention and reduction in disease risk, research also suggests that engaging in stimulating mental activity throughout adulthood builds cognitive and brain reserve and reduces dementia risk. Therefore, midlife (defined here as 40 to 65 years) may be a suitable time to introduce cognitive interventions for maintaining cognitive function and, in the longer term, possibly preventing or delaying the onset of clinical dementia. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for maintaining or improving cognitive function in cognitively healthy people in midlife. SEARCH METHODS: We searched up to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), the specialised register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG). We ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP at www.apps.who.int/trialsearch, to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people between 40 and 65 years of age (80% of study population within this age range). Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: For preliminary screening of search results, we used a 'crowd' method to identify RCTs. At least two review authors working independently screened remaining citations against inclusion criteria; independently extracted data; and assessed the quality of the included trial, using the Cochrane risk of bias assessment tool. We used GRADE to describe the overall quality of the evidence. MAIN RESULTS: We identified one eligible study that examined the effect of computerised cognitive training (CCT) in 6742 participants over 50 years of age, with training and follow-up duration of six months. We considered the study to be at high risk of attrition bias and the overall quality of the evidence to be low.Researchers provided no data on our primary outcome. Results indicate that there may be a small advantage for the CCT group for executive function (mean difference (MD) -1.57, 95% confidence interval (CI) -1.85 to -1.29; participants = 3994; low-quality evidence) and a very small advantage for the control group for working memory (MD 0.09, 95% CI 0.03 to 0.15; participants = 5831; low-quality evidence). The intervention may have had little or no effect on episodic memory (MD -0.03, 95% CI -0.10 to 0.04; participants = 3090; low-quality evidence). AUTHORS' CONCLUSIONS: We found low-quality evidence from only one study. We are unable to determine whether computerised cognitive training is effective in maintaining global cognitive function among healthy adults in midlife. We strongly recommend that high-quality studies be undertaken to investigate the effectiveness and acceptability of cognitive training in midlife, using interventions that last long enough that they may have enduring effects on cognitive and brain reserve, and with investigators following up long enough to assess effects on clinically important outcomes in later life.


Assuntos
Cognição , Disfunção Cognitiva/prevenção & controle , Instrução por Computador , Envelhecimento Saudável , Idoso , Demência/prevenção & controle , Humanos , Memória Episódica , Pessoa de Meia-Idade , Fatores de Tempo
15.
Neurobiol Aging ; 78: 64-73, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30877840

RESUMO

Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding variant within the DNA methyltransferase gene DNMT3L (R278G, A/G) by examining B vitamin intake, homocysteine levels, cognitive performance, and brain atrophy in individuals in the VITACOG study of mild cognitive impairment and the TwinsUK cohort. In the VITACOG study, individuals who received a 2-year treatment of B vitamins and carried the G allele showed better "visuospatial associative memory" and slower rates of brain atrophy. In the TwinsUK study, improved "visuospatial associative memory" was evident in individuals who reported regular vitamin intake and were A/A homozygotes. In silico modeling indicated that R278G disrupts protein interaction between DNMT3L and DNMT3A, affecting the DNMT3A-3L-H3 complex required for DNA methylation. These findings show that vitamin intake and genetic variation within DNMT3L interact to influence cognitive decline.


Assuntos
Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/genética , Complexo Vitamínico B/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Atrofia , Encéfalo/patologia , Cognição , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/psicologia , Feminino , Homocisteína/efeitos adversos , Homocisteína/metabolismo , Humanos , Masculino , S-Adenosilmetionina/metabolismo , Memória Espacial
16.
Int J Mol Sci ; 20(5)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845644

RESUMO

A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kß genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.


Assuntos
Antioxidantes/administração & dosagem , Disfunção Cognitiva/prevenção & controle , Metilação de DNA/efeitos dos fármacos , Resveratrol/administração & dosagem , Animais , Antioxidantes/farmacologia , Envelhecimento Cognitivo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Troca Materno-Fetal , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Gravidez , Regiões Promotoras Genéticas/efeitos dos fármacos , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos
17.
Anaesthesia ; 74(6): 741-750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30835822

RESUMO

Peri-operative dexmedetomidine can reduce rates of delirium immediately after surgery. We aimed to assess the effect of dexmedetomidine on cognition up to six postoperative months and its association with changes in serum concentrations of brain-derived neurotrophic factor on the third and seventh postoperative days. We randomly allocated 535 patients aged 65 years or more undergoing scheduled gastro-intestinal laparotomy to: intra-operative dexmedetomidine, 0.5 µg.kg-1 bolus followed by 0.4 µg.kg-1 .hr-1 infusion (n = 269), or placebo (n = 266). Dexmedetomidine reduced the rate of cognitive impairment: on the third postoperative day, 40/269 vs. 65/266, p = 0.006; on the seventh postoperative day, 31/269 vs. 49/266, p = 0.03 and at one postoperative month, 42/250 vs. 61/248, p = 0.04. Cognitive impairment at seven postoperative days was associated with changes in brain-derived neurotrophic factor concentrations on the third and seventh postoperative days; area under the receiver operating characteristic curve 0.63, p < 0.001 and 0.58, p = 0.016, respectively. Intra-operative dexmedetomidine reduced cognitive decline up to one postoperative month in elderly patients undergoing scheduled laparotomy, which was associated with changes in serum brain-derived neurotrophic factor.


Assuntos
Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/sangue , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/sangue , Estudos Prospectivos
18.
Cochrane Database Syst Rev ; 3: CD012277, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30864187

RESUMO

BACKGROUND: Increasing age is associated with a natural decline in cognitive function and is also the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or to reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and is intended to maintain optimum cognitive function. This review examines the effect of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for the maintenance or improvement of cognitive function in cognitively healthy people in late life. SEARCH METHODS: We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch) to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random-effect meta-analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS: We identified eight RCTs with a total of 1183 participants. Researchers provided interventions over 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had a moderate risk of bias. Review authors noted a lot of inconsistency between trial results. The overall quality of evidence was low or very low for all outcomes.We compared CCT first against active control interventions, such as watching educational videos. Because of the very low quality of the evidence, we were unable to determine any effect of CCT on our primary outcome of global cognitive function or on secondary outcomes of episodic memory, speed of processing, executive function, and working memory.We also compared CCT versus inactive control (no interventions). Negative SMDs favour CCT over control. We found no studies on our primary outcome of global cognitive function. In terms of our secondary outcomes, trial results suggest slight improvement in episodic memory (mean difference (MD) -0.90, 95% confidence interval (CI) -1.73 to -0.07; 150 participants; 1 study; low-quality evidence) and no effect on executive function (SMD -0.08, 95% CI -0.31 to 0.15; 292 participants; 2 studies; low-quality evidence), working memory (MD -0.08, 95% CI -0.43 to 0.27; 60 participants; 1 study; low-quality evidence), or verbal fluency (MD -0.11, 95% CI -1.58 to 1.36; 150 participants; 1 study; low-quality evidence). We could not determine any effects on speed of processing at trial endpoints because the evidence was of very low quality.We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS: We found little evidence from the included studies to suggest that 12 or more weeks of CCT improves cognition in healthy older adults. However, our limited confidence in the results reflects the overall quality of the evidence. Inconsistency between trials was a major limitation. In five of the eight trials, the duration of intervention was just three months. The possibility that longer periods of training could be beneficial remains to be more fully explored.


Assuntos
Cognição , Disfunção Cognitiva/prevenção & controle , Instrução por Computador , Envelhecimento Saudável , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Demência/prevenção & controle , Humanos , Memória Episódica , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
19.
Braz J Cardiovasc Surg ; 34(1): 76-84, 2019 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30810678

RESUMO

Postoperative cognitive dysfunction is a common complication following cardiac surgery. The incidence of cognitive dysfunction is more pronounced in patients receiving a cardiac operation than in those undergoing a non-cardiac operation. Clinical observations demonstrated that pulsatile flow was superior to nonpulsatile flow, and membrane oxygenator was superior to bubble oxygenator in terms of postoperative cognitive status. Nevertheless, cognitive assessments in patients receiving an on-pump and off-pump coronary artery bypass surgery have yielded inconsistent results. The exact mechanisms of postoperative cognitive dysfunction following coronary artery bypass grafting remain uncertain. The dual effects, neuroprotective and neurotoxic, of anesthetics should be thoroughly investigated. The diagnosis should be based on a comprehensive cognitive evaluation with neuropsychiatric tests, cerebral biomarker inspections, and electroencephalographic examination. The management strategies for cognitive dysfunction can be preventive or therapeutic. The preventive strategies of modifying surgical facilities and techniques can be effective for preventing the development of postoperative cognitive dysfunction. Investigational therapies may offer novel strategies of treatments. Anesthetic preconditioning might be helpful for the improvement of this dysfunction.


Assuntos
Disfunção Cognitiva/etiologia , Ponte de Artéria Coronária/efeitos adversos , Complicações Pós-Operatórias/etiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/prevenção & controle , Eletroencefalografia , Humanos , Testes Neuropsicológicos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco
20.
Mediators Inflamm ; 2019: 1236082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799999

RESUMO

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). Meanwhile, QTP also prevented the protein loss of the synaptic protein synaptophysin (SYP) and myelin basic protein (MBP). Here, our results indicate that QTP could inhibit neuroinflammatory response from glial cells and block the injury of released cytokines to neurons and oligodendrocytes in diabetic mice (DM). These beneficial effects could protect diabetic mice from the memory and cognitive deficit. QTP may be a potential treatment compound to handle the memory and cognitive dysfunction in diabetic patients.


Assuntos
Fumarato de Quetiapina/uso terapêutico , Animais , Astrócitos/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Transtornos Cognitivos/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Função Executiva/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Estreptozocina/toxicidade , Fator de Necrose Tumoral alfa/metabolismo
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