Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD.@*METHODS@#A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus.@*RESULTS@#There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).@*METHODS@#The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.@*RESULTS@#Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P0.05).@*CONCLUSIONS@#EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD.@*METHODS@#Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus.@*RESULTS@#Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (@*CONCLUSION@#Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Effect of early acupuncture on cognitive function in patients with vascular dementia after cerebral infarction / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of early acupuncture for vascular dementia (VD) after cerebral infarction, and explore its possible mechanism.@*METHODS@#A total of 120 patients with VD after cerebral infarction were randomized into an acupuncture combined with medication group (60 cases, 1 case dropped off) and a western medication group (60 cases, 1 case dropped off). In the western medication group, oxiracetam capsules were given orally, 2 capsules each time, 3 times a day. On the basis of the treatment as the western medication group, @*RESULTS@#The total effective rate was 89.8% (53/59) in the acupuncture combined with medication group, which was superior to 76.3% (45/59) in the western medication group (@*CONCLUSION@#Early acupuncture could improve cognitive function and activities of daily living in patients with VD after cerebral infarction, its mechanism may be related to improving the blood flow velocity of MCA, promoting blood circulation, and improving cerebral perfusion.

Nuevos términos clínicos, prevención y tratamiento del trastorno cognitivo vascular: revisión de literatura basada en la evidencia / New clinical terms, prevention and treatment of vascular cognitive impairment: a review of evidence-based literature

El trastorno cognitivo vascular agrupa todas las instancias donde el compromiso cognitivo puede ser atribuidoa enfermedad vascular cerebral, es mayor que el esperado para el envejecimiento normal y que, cuando llega aafectar las actividades de la vida diaria, se denomina demencia vascular. En esta revisión, se actualizan los términos relacionados a trastorno cognitivo vascular y se plantean estrategias de prevención y tratamiento basadas en revisiones sistemáticas y meta-análisis. En la primera parte se definen diversos términos relacionados a trastorno cognitivo vascular; en la segunda, se plantea el tratamiento del trastorno cognitivo vascular/demencia vascular, que incluyeun manejo orientado a prevención primaria, controlando los factores de riesgo; un tratamiento secundario paraprevenir la exacerbación o la extensión de las lesiones producidas por la injuria vascular cerebral y, finalmente, untratamiento terciario o sintomático de los problemas cognitivos y/o conductuales. Damos especial énfasis y se fundamenta la conveniencia y beneficios de los tratamientos primario y secundario.

Vascular cognitive impairment is a label ascribed to cases in which the cognitive impairment can be attributed to cerebral vascular disease, is greater than the expected for normal aging and, when affecting the activities of daily life, is called vascular dementia. In this review, the terms related to vascular cognitive impairment, are updated, and strategies for prevention and treatment, based on systematic reviews and meta-analyses are outlined. In the first part, various vascular cognitive impairment-related terms are defined; in the second part, the treatment of vascular cognitive impairment / vascular dementia is described: it includes, management steps oriented towards primary prevention, controlling risk factors; a secondary treatment aimed at the prevention of exacerbation or extension of lesions produced by the vascular brain injuries and, finally, the tertiary or symptomatic treatment of cognitive and / or behavioral manifestations. Special emphasis is placed on, and the convenience and benefits of the primary and secondary treatments are substantiated.

Depressão vascular no idoso: resposta ao tratamento antidepressivo associado a inibidor das colinesterases / Vascular depression in elderly: response to treatment with antidepressant associated to cholinesterase inhibitor

CONTEXTO: Entre os transtornos neuropsiquiátricos ocasionados por eventos cerebrovasculares, a depressão vascular é pouco diagnosticada por médicos não especialistas, causando aumento da morbimortalidade de pacientes idosos. CASO CLÍNICO: Trata-se de um paciente com 67 anos que apresentou resposta parcial a tratamento com inibidores da recaptura de serotonina e efeitos adversos autonômicos graves com outros antidepressivos. A adição de rivastigmina ao citalopram promoveu sucesso terapêutico, com redução de 23 para 7 pontos, na escala de Hamilton para depressão. DISCUSSÃO: O resultado obtido traz novas perspectivas para o tratamento da depressão vascular, sendo necessários ensaios clínicos controlados que evidenciem o benefício da adição dos inibidores das colinesterases aos antidepressivos no tratamento destes pacientes.

CONTEXT: Among neuropsychiatric disorders caused by cerebrovascular factors, vascular depression is diagnosed in a small degree by general practitioners, causing morbid-mortality increase in elderly. CASE REPORT: That is a case of a 67 year-old-man with partial response after treatment with a Selective Serotonin Receptors Inhibitor, and severe autonomic adverse effects with other antidepressants. The addition of rivastigmine to citalopram resulted in a therapeutic success, with a reduction of 23 to 7 points on the Hamilton Depressive Scale (HAM-D). DISCUSSION: The result obtained brings new perspectives to the treatment of vascular depression, providing that randomized controlled trials with larger sample sizes confirm the positive effect of the addition of a cholinesterase inhibitor to antidepressants in the treatment of these patients.

Demencia mista: do conceito ao tratamento / Mixed dementia: from concept to treatment

A demência mista (DM) é uma condição ainda mal definida cuja importância vem se afirmando cada vez mais. Corresponde a um quadro resultante da associação da doença de Alzheimer (DA) e do comprometimento cognitivo vascular/demência vascular (CCV/DV). É uma demência relativamente prevalente, principalmente no idoso. A fisiopatologia é especialmente importante para melhor compreensão da gênese do quadro clínico. A expressão clínica da DA é sequenciada e previsível, de acordo com o estágio anatomoclínico. Já a CCV/DV expressa-se de modo variado, na dependência da localização e extensão da(s) lesão(ões) subjacente(s). Assim, as manifestações clínicas da DM, correspondem às da DA em um determinado estágio associadas às de um determinado quadro de CCV/DV. O diagnóstico nem sempre é fácil e frequentemente não é considerado, porém com a afirmação da definição e com os critérios diagnósticos clínicos e os numerosos recursos laboratoriais disponíveis, deverá certamente ser feito com maior rigor e frequência. A DM conta com um leque de opções terapêuticas, em vários níveis, desde a prevenção, até o estacionamento ou melhora do quadro instalado, porém na dependência da combinação patológica subjacente. A prevenção, assim como o estacionamento e a melhora do componente vascular pode eventualmente ser obtida através do controle de certo número de fatores de risco, compartilhados em grande parte pelo componente degenerativo. Além disso, pode se utilizar a estratégia colinérgica, para melhora da cognição e a glutamatérgica, que também contribui na neuroproteção. As estratégias monoaminérgicas e outras relacionadas frequentemente são necessárias para o controle de sintomas de comportamento e psicológicos. Assim, a DM é quadro passível de tratamento, com recursos variadas e eficazes, sendo frequentemente gratificante no que diz respeito aos resultados obtidos, embora na dependência da extensão das patologias subjacentes.

Mixed dementia (MD) is a yet ill-defined condition that is receiving growing recognition. Corresponds to a picture resulting from the combination of Alzheimer's disease (AD) and vascular cognitive impairment/vascular dementia (VCI/VaD). it is a relatively prevalent dementia, mainly in the aged. The pathophysiology is especially important for a better understanding of the genesis of the clinical picture. The clinical expression of AD is sequential and previsible, according to the anatomo-clinical stage. On the other hand, VCI/VaD is expessed in a varied way, depending on the localization and extension of the underlying lesion(s). Thus, the clinical manifestations of MD correspond to those of a given stage of AD combined with those of a given picture of VCI/Vad. The diagnosis is not always easy and frequently it is even not considered, but with the affirmation of the definition and the availability of diagnostic clinical criteria and the numerous laboratorial resources, it will certainly be established with increasing accuracy and frequency. There is a wide range of therapeutic options for MD, in several levels, from prevention to interruption or improvement of the established picture, but on the dependence of the underlying pathological combination. The prevention, as well as the stabilization and improvement of the vascular component can eventually be obtained through the control of a number of risk factors, most of them shared by the degenerative component. Additionally, cholinergic strategy to enhance cognition, and the glutamatergic one that contributes also for neuroprotection can be used. The monoaminergic and related strategies are frequently necessary for the control of behavioral and psychological symptoms. Thus, MD is a condition amenable to varied and effective therapeutic possibilities, frequently rewarding in face of the obtained results, but depending on the extension of the underlying pathologies.

Demência vascular: dificuldades diagnósticas e tratamento / Vascular dementia: a critical review of diagnosis and treatment

Justificativa: O tratamento dos pacientes com síndrome demencial depende do diagnóstico correto de sua etiologia e da utilizaçao de critérios objetivos de avaliaçao do curso da doença. O diagnóstico preciso da demência vascular (Dva) é difícil e nossos conhecimentos sobre a organizaçao neuropsicológica do cérebro em estados de doença e a evoluçao da doença sao precários, tornando penosa a avaliaçao das respostas a diferentes intervençoes. Métodos: Sao discutidos os critérios diagnósticos, os instrumentos de avaliaçao do curso da Dva e as diferentes intervençoes terapêuticas atualmente em estudo. Resultados: O uso de critérios diagnósticos estritos e a otimizaçao dos métodos de avaliaçao evolutiva sao passos importantes para otimizar o tratamento dos pacientes com DVa. A prevençao de novos eventos cerebrovasculares é a única medida comprovadamente eficaz para promover estabilizaçao e talvez regressao das alteraçoes cognitivas e comportamentais nestes pacientes. As evidências de possível benefício de estimulantes inespecíficos do metabolismo cerebral e de drogas neuroprotetoras nao sao suficientes para indicar seu uso rotineiro. Medidas de estruturaçao do ambiente, o uso racional e parcimonioso de medicamentos em geral, e a definiçao através de testes neuropsicológicos de rotas terapêuticas adaptadas às necessidades de cada paciente sao também importantes. Conclusoes: Critérios diagnósticos e de acompanhamento evolutivo da DVa sao ainda inadequados. A prevençao de novos episódios cerebrovasculares é a base do tratamento dos pacientes com DVa. O uso criterioso de drogas psiquiátricas , uma abordagem neurocognitiva dirigida aos déficits de cada paciente e a estruturaçao do ambiente para reduzir demandas desnecessárias e cansaço sao importantes medidas complementares, mas deixam grande margem para otimizaçao do tratamento.

Demencia-seudodemencia-estados confusionales / Dementia-pseudodementia-confusional states

Los desórdenes mentales son extremadamente comunes e importantes en el anciano. La demencia es el problema más delicado y ocurre en 10 por ciento de aquellos por encima de los 65 años. La demencia senil es el tipo más frecuente sin embargo es la de tratamiento menos satisfactorio. Las demencias arterioescleróticas y secundarias son más suceptibles de tratamiento siempre que sea detectada a tiempo. El examen apropiado y estudios de laboratorio son importantes elementos de estudios tanto que procesos potencialmente tratables pueden ser manejados tempranamente. Los estados depresivos o seudo-demencia así como los estados tóxicos confucionales pueden llevar a confusión en el examinador, cuando el mismo antepone la edad cronológica del paciente a la realización de una evaluación clínica exaustiva justificando muchas veces a través sólo de este detalle el diagnóstico de demencia senil en el paciente