Anesthesia and Alzheimer disease - Current perceptions / Anestesia e doença de Alzheimer - Percepções atuais

Abstract Background and objectives: It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre-clinical and clinical data related to anesthesia and this disease. Content: Alzheimer disease affects about 5% of the population over 65 years old, with age being the main risk factor and being associated with a high morbidity. Current evidence questions a possible association between anesthesia, surgery, and long-term cognitive effects, including Alzheimer disease. Although data from some animal studies suggest an association between anesthesia and neurotoxicity, this link remains inconclusive in humans. We performed a review of the literature in which we selected scientific articles in the PubMed database, published between 2005 and 2016 (one article from 1998 due to its historical relevance), in English, which address the possible relationship between anesthesia and Alzheimer disease. 49 articles were selected. Conclusion: The possible relationship between anesthetic agents, cognitive dysfunction, and Alzheimer disease remains to be clarified. Prospective cohort studies or randomized clinical trials for a better understanding of this association will be required.

Resumo Justificativa e objetivos: Tem sido especulado que o uso de agentes anestésicos possa ser um fator de risco para o desenvolvimento de doença de Alzheimer. O objetivo desta revisão é descrever e discutir dados pré-clínicos e clínicos relacionados com a anestesia e essa doença. Conteúdo: A doença de Alzheimer afeta cerca de 5% da população com mais de 65 anos, a idade é o principal fator de risco e está associada a uma elevada morbidade. A evidência atual questiona uma possível associação entre anestesia, cirurgia e efeitos cognitivos em longo prazo, o que inclui a doença de Alzheimer. Embora os dados obtidos em alguns dos estudos animais sugiram uma associação entre anestesia e neurotoxicidade, esse elo permanece inconclusivo em humanos. Fizemos uma revisão da literatura em que foram selecionados artigos científicos na base de dados Pubmed, publicados entre 2005 e 2016 (um de 1998 pela relevância histórica), em inglês, que abordam a eventual relação entre anestesia e doença de Alzheimer. Foram eleitos 49 artigos. Conclusão: A possível relação entre agentes anestésicos, disfunção cognitiva e doença de Alzheimer permanece por esclarecer. Serão necessários estudos de coorte prospetivos ou ensaios clínicos randomizados para melhor compreensão dessa associação.

Effect of ethanolic extract of Coriandrum sativum L. on tacrine induced orofacial dyskinesia.

The effect of ethanolic extract of Coriandrum sativum L. seeds (100, 200 mg/kg) was studied on tacrine induced orofacial dyskinesia. Tacrine (2.5 mg/kg, i.p.) treated animals were observed for vacuous chewing movements (VCM), tongue protrusions (TP) and orofacial bursts (OB) for 1 h followed by observations for locomotor changes and cognitive dysfunction. Sub-chronic administration of Coriandrum sativum L. seed extract (E-CS) (100, 200 mg/kg, p.o., for 15 days significantly (P <0.05) decreased the tacrine induced VCM, TP and OB; and also significantly (P <0.05), increased locomotion and cognition compared to the tacrine treated group. Biochemical analysis revealed that tacrine administration significantly (P <0.05) decreased the levels of superoxide dismutase (SOD), Catalase (CAT), glutathione reductase (GSH) levels and also significantly (P <0.05) increased lipid peroxidation (LPO) as an index of oxidative stress, whereas sub-chronic administration of E-CS significantly (P <0.05) improved the antioxidant enzyme (i.e. SOD, CAT, and GSH) levels and also significantly (P <0.05) decreased lipid peroxidation (LPO). The results have demonstrated the protective role of ethanolic extract of Coriandrum sativum. L against tacrine induced orofacial dyskinesia.

Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.

Neurobiological effect of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in experimental paradigm of Alzheimer’s disease.

Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.

Neuroprotective potential of ethanolic extract of Pseudarthria viscida (L) Wight and Arn against -amyloid(25-35)-induced amnesia in mice.

The neuroprotective potential of ethanolic extract of roots of Pseudarthria viscida (L) Wight and Arn (EEPV) was investigated against -amyloid(25-35)-induced amnesia in mice which is a suitable animal model for Alzheimer’s disease (AD). The senile plaques of -amyloid (A) are major constituents accumulated during the progression of AD as a potent neurotoxicant. In our investigation, intracerebroventricular injection of A(25-35) in mice induced the neurodegeneration, exhibited the increased time of escape latency in behavioral pattern using water maze and decreased the levels of antioxidants namley superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and vitamin C with elevated level of acetylcholinesterase enzyme (AChE). The neuroprotective potential of EEPV was determined by behavioral pattern using water maze and biochemical parameters such as SOD, CAT and GPx and vitamin C content as well as AChE. Mice were treated with EEPV at 200 and 400 mg/kg doses for 21 days. Except control, all animals received a single injection of neurotoxicant A(25-35) on 14th day. In behavioural assessment, treatment with ethanolic extract improved the cognitive function in the water maze and attenuated the elevated levels of AChE with increase in antioxidant enzymes, indicating the neuroprotection with increased levels of vitamin C. These findings suggest that ethanolic extract of P. viscida exerts anti-amnesiac effects and enhances cognitive function.

Molecular toxicity of aluminium in relation to neurodegeneration.

Exposure to high levels of aluminium (Al) leads to neurofibrillary degeneration and that Al concentration is increased in degenerating neurons in Alzheimer's disease (AD). Nevertheless, the role of Al in AD remains controversial and there is little proof directly interlinking Al to AD. The major problem in understanding Al toxicity is the complex Al speciation chemistry in biological systems. A new dimension is provided to show that Al-maltolate treated aged rabbits can be used as a suitable animal model for understanding the pathology in AD. The intracisternal injection of Al-maltolate into aged New Zealand white rabbits results in pathology that mimics several of the neuropathological, biochemical and behavioural changes as observed in AD. The neurodegenerative effects include the formation of intraneuronal neurofilamentous aggregates that are tau positive, oxidative stress and apoptosis. The present review discusses the role of Al and use of Al-treated aged rabbit as a suitable animal model to understand AD pathogenesis.

Brazilian female crack users show elevated serum aluminum levels

OBJECTIVE: There is no information in the literature on the impact of crack smoking using crushed aluminum cans as makeshift pipes, a common form of crack use in Brazil. Since aluminum intake is associated with neurological damage, we measured serum aluminum levels in crack smokers. The objective of this study was to ascertain the levels of aluminum in crack users who smoke on makeshift aluminum pipes. METHOD: 71 female crack smokers, their mean age being 28.0 (± 7.7), provided information about their drug use, and had blood samples tested for serum aluminum level. RESULTS: 56 (79 percent) subjects smoked crack from crushed can pipes, while 15 (21 percent) smoked from other containers. Fifty-two (73.2 percent) out of the 71 subjects presented a serum aluminum level of 2 æg/l and 13 (18.3 percent) had a serum aluminum level of 6 æg/l cut-off point, which is above the reference value. When compared to non-drug users matched by their mean age and gender, they had similar median values and interquartile ranges for serum aluminum level [3 (2-4.6) for crack smokers; 2.9 (1.6-4.1) for controls], but with different means and standard deviations (4.7 ± 4.9 and 2.9 ± 1.7, respectively). DISCUSSION: Crack smokers have high serum aluminum level, but we are unsure of its complete association with aluminum cans. Further studies are needed. If such association is proven true in future research, further issues will be raised in dealing with this important disorder, including proper planning and evaluation of public health policies in this area.

OBJETIVO: Não há informação na literatura sobre o impacto do uso de crack fumado em latas de alumínio utilizadas como cachimbos improvisados, uma forma comum de uso de crack no Brasil. Uma vez que a ingestão de alumínio está associada a dano neurológico, nós medimos alumínio sérico em usuários de crack. O objetivo deste estudo foi avaliar os níveis de alumínio em usuários de crack que fumam em cachimbos improvisados de lata de alumínio. MÉTODO: Setententa e uma usuárias de crack, com média de idade de 28,0 anos (± 7,7), forneceram informação sobre seu uso de drogas e tiveram amostras de seu sangue testadas para níveis séricos de alumínio. RESULTADOS: Cinqüenta e seis (79 por cento) sujeitos fumaram crack usando cachimbos de lata e 15 (21 por cento) fumaram em outros formatos. Cinqüenta e dois (73,2 por cento) dos 71 sujeitos apresentaram níveis de alumínio sérico de 2 æg/l e 13 (18,3 por cento) tinham níveis no ponto de corte 6 æg/l, o que está acima dos valores de referência. Quando comparados com não-usuários pareados por média de idade e do mesmo gênero, os sujeitos tiveram valores medianos e intervalos inter-quartil para níveis séricos similares [3 (2-4,6) para usuários de crack; 2,9 (1,6-4,1) para os controles], porém com médias e desvios-padrão diferentes (4,7 ± 4,9 e 2,9 ± 1,7, respectivamente). DISCUSSÃO: Usuários de crack apresentam altos níveis de alumínio sérico, mas não temos certeza disto estar associado completamente com as latas de alumínio. Mais estudos são necessários. Se tal associação se mostrar verdadeira em pesquisa no futuro, questões terão que ser debatidas a respeito deste problema, incluindo planejamento apropriado e avaliação das políticas públicas nesta área.

Alelos do gene LRP associados ao risco genético da doença de Alzheimer em população exposta ao aluminío / Alleles of the LRP gene associated to the genétic risk of Alzheimer's Disease in population exposed to aluminum

Objetivo:Quantificar os alelos do polimorfismo 766C/T do gene LRP em indivíduos moradores do Lago Batata, expostos à contaminação por Al, e em indivíduos-controle nas comunidades do lago Erepecu e Arancuã pertencentes ao município de oriximiná (Pará). Método: Utilizou-se a técnica de PCR seguida de digestão enzimática com enzima apropriada(Rsal) na análise molecular. Extraiu-se o DNA das amostras de sangue coletadas de 40 moradores do Lago Batata e de 36 indivíduos-controle. Resultados: Em todoas as comunidades, o genótipo C/C e o alelo C mostraram-se os mais comuns, com freqüências superiores a 69 por cento e 80 por cento, respectivamente. Conclusão: A maior prevalência do genótipo C/C pode sugerir a existência de risco genético aumentado para o desenvolvimento da DA. Em relação à população do Lago Batata, particularmente, esse risco pode ser potencializado pela contaminação por alumínio

Aspectos bioquímicos en la enfermedad de Alzheimer / Biochemical aspects in Alzheimer's disease

La enfermedad de Alzheimer es una demencia cortical primaria con una prevalencia de 2.4 por ciento antes de los 75 años y de 10.9 por ciento después de esta edad. Representa el 40 a 50 por ciento de todas las demencias y es un padecimiento degenerativo irreversible. Importantes avances epidemiológicos, genéticos, patológicos y bioquímico-moleculares serán la base de todos los abordajes terapéuticos en un futuro próximo. El presente trabajo enumera y profundiza algunas de las alteraciones bioquímicas involucradas en su etiopatogénesis, explica los hallazgos primarios o secundarios al proceso de degeneración neurocerebral sin soslayar múltiples propuestas que figuran ya como pilares y directrices en el conocimiento de esta enfermedad