Tu-Xian Decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1 / 中国天然药物

Tu-Xian decoction (TXD), a traditional Chinese medicine (TCM) formula, has been frequently administered to manage diabetic cognitive impairment (DCI). Despite its widespread use, the mechanisms underlying TXD's protective effects on DCI have yet to be fully elucidated. As a significant regulator in neurodegenerative conditions, death-associated protein kinase-1 (DAPK-1) serves as a focus for understanding the action of TXD. This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1. To this end, a diabetic model was established using Sprague-Dawley (SD) rats through a high-fat, high-sugar (HFHS) diet regimen, followed by streptozotocin (STZ) injection. The experimental cohort was stratified into six groups: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD groups. Following a 12-week treatment period, various assessments-including blood glucose levels, body weight measurements, Morris water maze (MWM) testing for cognitive function, brain magnetic resonance imaging (MRI), and histological analyses using hematoxylin-eosin (H&E), and Nissl staining-were conducted. Protein expression in the hippocampus was quantified through Western blotting analysis. The results revealed that TXD significantly improved spatial learning and memory abilities, and preserved hippocampal structure in diabetic rats. Importantly, TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region. These results underscore TXD's potential in mitigating DCIvia DAPK-1 inhibition, positioning it as a viable therapeutic candidate for addressing this condition. Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through α 7nAChR-Induced Autophagy / 中国结合医学杂志

OBJECTIVES@#To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats.@*METHODS@#The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively.@*RESULTS@#ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01).@*CONCLUSION@#ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.

A prática da contenção em idosos: revisão integrativa / La práctica de la contención en ancianos: revisión integradora / The practice of containment in the elderly: an integrative review

Resumo Objetivo Analisar as evidências da literatura sobre a prática da contenção em idosos. Métodos Revisão integrativa de literatura, com busca dos estudos primários publicados de 2013 a 2017, realizada nas bases de dados eletrônicas LILACS e MEDLINE, nos meses de maio e junho de 2018. As buscas foram obtidas pelo cruzamento, nas bases de dados, dos seguintes descritores e palavras: contenção; restrição; restrição física; e idoso. Resultados Foram incluídos 17 artigos e, a análise indicou que as evidências disponíveis na literatura reportam à prática de contenções no cotidiano de idosos, às consequências frente ao uso de contenções em idosos, e a técnicas alternativas ao uso das contenções. Conclusões O uso de contenções, principalmente físicas e químicas, é permeado por maior probabilidade de declínio cognitivo do idoso, além de consequências à saúde física e psicológica, podendo, até mesmo, resultar em óbito. Programas de intervenção e políticas designadas à diminuição do uso de contenções em idosos mostram-se como estratégias alternativas, contribuindo assim, para a qualificação da assistência.

Resumen Objetivo analizar las evidencias de la literatura sobre la práctica de la contención en ancianos. Métodos revisión integradora de literatura, con búsqueda de los estudios primarios publicados de 2013 a 2017, realizada en las bases de datos electrónicas LILACS y MEDLINE, en los meses de mayo y junio de 2018. Las búsquedas fueron obtenidas por el cruce de los siguientes descriptores y palabras en las bases de datos: contención, restricción, restricción física y anciano. Resultados se incluyeron 17 artículos y el análisis indicó que las evidencias disponibles en la literatura se refieren a la práctica de contenciones en el cotidiano de los ancianos, a las consecuencias frente al uso de contenciones en ancianos y a las técnicas alternativas al uso de contenciones. Conclusiones el uso de contenciones, principalmente físicas y químicas, está impregnado de una mayor probabilidad de deterioro cognitivo del anciano, además de consecuencias en la salud física y psicológica, lo que puede, inclusive, derivar en óbito. Programas de intervención y políticas designadas a la reducción del uso de contenciones en ancianos se muestran como estrategias alternativas y, de este modo, contribuyen a la cualificación de la atención.

Abstract Objective To analyze the literature evidence on the practice of containment in the elderly. Methods Integrative literature review, searching for primary studies published from 2013 to 2017, conducted in the electronic databases of LILACS and MEDLINE, in the months of May and June of 2018. The searches were obtained by crossing the descriptors and words: containment; restriction; physical restraint; and elderly. Results A total of 17 articles were included, and the analysis indicated that the available evidence in the literature reports to the practice of restraints in the daily life of the elderly, the consequences for use of restraints in the elderly, and alternative techniques to the use of restraints. Conclusion The use of restraints, mainly physical and chemical, is permeated by a higher probability of cognitive decline of the elderly, as well as physical and psychological health consequences, and can even result in death. Intervention programs and policies designed to reduce the use of restraints in the elderly are shown as alternative strategies, contributing to the qualification of care.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

Traumatic brain injury pharmacological treatment: recommendations / Tratamento farmacológico do traumatismo cranioencefálico: recomendações

ABSTRACT This article presents the recommendations on the pharmacological treatment employed in traumatic brain injury (TBI) at the outpatient clinic of the Cognitive Rehabilitation after TBI Service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. A systematic assessment of the consensus reached in other countries, and of articles on TBI available in the PUBMED and LILACS medical databases, was carried out. We offer recommendations of pharmacological treatments in patients after TBI with different symptoms.

RESUMO Este artigo apresenta as recomendações sobre o tratamento farmacológico empregado para o traumatismo cranioencefálico (TCE) em pacientes ambulatoriais de Reabilitação Cognitiva pós-TCEno Serviço do HCFMUSP Foi realizada uma avaliação sistemática dos consensos publicados em outros países e dos artigos sobre TCE disponíveis nas bases de periódicos médicos como PUBMED e LILACS. Recomendamos tratamentos farmacológicos em pacientes pós-TCE com diferentes sintomas.