Neuroprotective effects of Tradescantia spathacea tea bioactives in Parkinson's disease: In vivo proof-of-concept.

Background and aim: Tradescantia spathacea (T. spathacea) is a traditional medicinal plant from Central America and its tea, obtained by infusion, has been recognized as a functional food. The aim of this work was to investigate the effects of dry tea containing biocompounds from T. spathacea tea on motor and emotional behavior, as well as tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression in 6-hydroxydopamine (6-OHDA)-lesioned rats. Experimental procedure: Bioactives were identified by Ultra Performance Liquid Chromatography (UPLC) and an in vivo study in male Wistar rats was run as proof of concept of neuroprotective effects of DTTS. Results and conclusion: We found 15 biocompounds that had not been previously reported in T. spathacea: the UPLC-QTOF-MS/MS allowed identification five phenolic acids, one coumarin, two flavonoids, one iridoid, one phenylpropanoid glycoside, and six fatty acid derivatives. The dry tea of T. spathacea (DTTS) presented significant antioxidant activity and high contents of phenolic compounds and flavonoids. Doses of 10, 30, and 100 mg/kg of DTTS were protective against dopaminergic neurodegeneration and exhibited modulatory action on the astrocyte-mediated neuroinflammatory response. Behavioral tests showed that 30 mg/kg of DTTS counteracted motor impairment, while 100 mg/kg produced an anxiolytic effect. The DTTS could be, therefore, a promising strategy for the management of Parkinson's disease.

New role of astrocytes in neuroprotective mechanisms after ischemic stroke / Novo papel dos astrócitos nos mecanismos neuroprotetores após acidente vascular cerebral isquêmico

Abstract Astrocytes are the most abundant cell subtypes in the central nervous system. Previous studies believed that astrocytes are supporting cells in the brain, which only provide nutrients for neurons. However, recent studies have found that astrocytes have more crucial and complex functions in the brain, such as neurogenesis, phagocytosis, and ischemic tolerance. After an ischemic stroke, the activated astrocytes can exert neuroprotective or neurotoxic effects through a variety of pathways. In this review, we will discuss the neuroprotective mechanisms of astrocytes in cerebral ischemia, and mainly focus on reactive astrocytosis or glial scar, neurogenesis, phagocytosis, and cerebral ischemic tolerance, for providing new strategies for the clinical treatment of stroke.

Resumo Os astrócitos são os subtipos de células mais abundantes no sistema nervoso central. Estudos anteriores acreditavam que os astrócitos são células de suporte no cérebro, que apenas fornecem nutrientes para os neurônios. No entanto, estudos recentes descobriram que os astrócitos têm funções mais cruciais e complexas no cérebro, como neurogênese, fagocitose e tolerância isquêmica. Após um acidente vascular cerebral isquêmico, os astrócitos ativados podem exercer efeitos neuroprotetores ou neurotóxicos através de uma variedade de vias. Nesta revisão, discutiremos os mecanismos neuroprotetores dos astrócitos na isquemia cerebral, e focaremos principalmente na astrocitose reativa ou cicatriz glial, neurogênese, fagocitose e tolerância isquêmica cerebral, para fornecer novas estratégias para o tratamento clínico do acidente vascular cerebral.

Neuroprotective effect of low mean arterial pressure on postoperative cognitive deficit attenuated by prolonged coronary artery bypass time: a meta-analysis

Abstract Introduction: The true influence of the low mean arterial pressure (low MAP) during coronary artery bypass grafting (CABG) on the development of postoperative cognitive deficit (POCD) remains controversial. We aimed to perform a meta-analysis and meta-regression to determine the effect of low MAP on POCD, as well as moderator variables between low MAP and POCD. Methods: The Web of Science, PubMed database, Scopus and the Cochrane Library database (up to June 2018) were searched and retrieved articles systematically reviewed. Only randomized controlled trials (RCTs) comparing maintenance of low MAP (<80 mmHg) and high MAP (>80 mmHg) during cardiopulmonary bypass (CPB) were included in our final review. Statistical analysis of the risk ratio (RR) and corresponding 95% confidence interval (CI) was used to report the overall effect. The overall effect and meta-regression analysis were done using Mantel-Haenszel risk ratio (MHRR) and the corresponding 95% confidence interval (CI). Results: A total of 731 patients in three RCTs were included in this study. POCD occurred in 6.4% of all cases. Maintenance of low MAP did not reduce the occurrence of POCD (MHRR 1.012 [95% CI 0.277-3.688]; Z=0.018; P=0.986; I2=66%). Shorter CPB time reduced the occurrence of POCD regardless of group assignment (MH log risk ratio -0.519 [95% CI -0.949 - -0.089]; Z= -2.367; P=0.017). Conclusion: POCD is a common event among CABG patients. The neuroprotective effect of low MAP on POCD was attenuated by the prolonged CPB time.

Neuroprotective Effect of Low Mean Arterial Pressure on Postoperative Cognitive Deficit Attenuated by Prolonged Coronary Artery Bypass Time: A Meta-Analysis.

INTRODUCTION: The true influence of the low mean arterial pressure (low MAP) during coronary artery bypass grafting (CABG) on the development of postoperative cognitive deficit (POCD) remains controversial. We aimed to perform a meta-analysis and meta-regression to determine the effect of low MAP on POCD, as well as moderator variables between low MAP and POCD. METHODS: The Web of Science, PubMed database, Scopus and the Cochrane Library database (up to June 2018) were searched and retrieved articles systematically reviewed. Only randomized controlled trials (RCTs) comparing maintenance of low MAP (<80 mmHg) and high MAP (>80 mmHg) during cardiopulmonary bypass (CPB) were included in our final review. Statistical analysis of the risk ratio (RR) and corresponding 95% confidence interval (CI) was used to report the overall effect. The overall effect and meta-regression analysis were done using Mantel-Haenszel risk ratio (MHRR) and the corresponding 95% confidence interval (CI). RESULTS: A total of 731 patients in three RCTs were included in this study. POCD occurred in 6.4% of all cases. Maintenance of low MAP did not reduce the occurrence of POCD (MHRR 1.012 [95% CI 0.277-3.688]; Z=0.018; P=0.986; I2=66%). Shorter CPB time reduced the occurrence of POCD regardless of group assignment (MH log risk ratio -0.519 [95% CI -0.949 - -0.089]; Z= -2.367; P=0.017). CONCLUSION: POCD is a common event among CABG patients. The neuroprotective effect of low MAP on POCD was attenuated by the prolonged CPB time.

ADENOSINE A1 RECEPTOR AGONIST PROTECTS AGAINST HIPPOCAMPAL NEURONAL INJURY AFTER LITHIUM CHLORIDE-PILOCARPINE-INDUCED EPILEPSY.

BACKGROUND: Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. MATERIALS AND METHODS: A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. RESULTS: In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). CONCLUSIONS: AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.

Adenosine a1 receptor agonist protects against hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy

Abstract Background Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. Materials and Methods A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. Results In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). Conclusions AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.

Neuroproteção fetal: uma utilização contemporânea do sulfato de magnésio / Fetal neuroprotection: a contemporary use of magnesium sulfate

Os principais usos contemporâneos do sulfato de magnésio na prática obstétrica incluem a prevenção e o tratamento de convulsões em portadoras de pré-eclâmpsia e eclâmpsia, o prolongamento da gravidez para administração antenatal de corticosteroides e a neuroproteção fetal na iminência de interrupção prematura da gestação, uma indicação mais recente. A paralisia cerebral é a causa mais comum de deficiência motora na infância e apresenta como fator de risco mais importante o nascimento pré-termo, cuja incidência tem aumentado significativamente. Como consequência, a ocorrência da paralisia cerebral também tem aumentado, a despeito da melhoria da sobrevida dos fetos pré-termos. No atual contexto de procura por estratégias que se mostrem efetivas na redução da paralisia cerebral nos recém-nascidos prematuros e que deveriam ser implementadas com o objetivo de diminuir os seus efeitos danosos nos indivíduos e suas famílias, nos serviços de saúde e na sociedade como um todo, o sulfato de magnésio tem se mostrado como o mais promissor agente neuroprotetor fetal. Desde a década de 1990, estudos resultantes das suas indicações para a prevenção das convulsões eclâmpticas ou para tocólise têm evidenciado redução nas taxas de paralisia cerebral e leucomalácia periventricular em prematuros. Diretrizes nacionais e internacionais mais recentes, baseando-se em resultados de ensaios randomizados controlados e metanálises de boa qualidade, têm avançado na recomendação sobre os regimes terapêuticos e na construção de algoritmos para utilização do sulfato de magnésio na neuroproteção fetal.(AU)

The main contemporary uses of magnesium sulfate in obstetric practice include the prevention and treatment of seizures in patients with preeclampsia and eclampsia, prolongation of pregnancy for antenatal administration of corticosteroids and fetal neuroprotection at the imminence of premature termination of pregnancy, a more recent indication. Cerebral palsy is the most common cause of motor deficits in childhood and has a significant increase in preterm birth as a major risk factor. As a result, the occurrence of cerebral palsy has also increased, despite the improvement in the survival of preterm fetuses. In the current context of search for strategies that are effective in reducing cerebral palsy in preterm newborns and that should be implemented with the aim of reducing their harmful effects on individuals and their families, health services and society as a whole, magnesium sulfate has been shown to be the most promising fetal neuroprotective agent. Since the 1990s, studies arising from its indications for prevention of eclamptic seizures or tocolysis have shown a reduction in the rates of cerebral palsy and periventricular leukomalacia in preterm infants. More recent national and international guidelines, based on results from randomized controlled trials and good quality meta-analyzes, have advanced the recommendation on therapeutic regimens and the construction of algorithms for the use of magnesium sulphate in fetal neuroprotection.(AU)

Aproximación a la farmacología del sulfato de magnesio desde la perspectiva obstétrica / An approach to the pharmacology of magnesium sulfate from an obstetric perspective / Abordagem farmacológica do sulfato de magnésio apartir da perspectiva obstétrica

Introducción: Desde su primer uso en 1926 en el manejo de la eclampsia el sulfato de magnesio ha sido un medicamento utilizado y estudiado ampliamente por obstetras. Durante mucho tiempo se mantuvo escepticismo sobre sus potenciales beneficios, pero la aparición de estudios bien estructurados aportó evidencia a favor o en contra de algunos de estos. Objetivo: Realizar una revisión de la literatura acerca dela farmacología, fisiología, farmacocinética, mecanismos de acción, principales usos y regímenes de administración del sulfato de magnesio en obstetricia. Metodología: Búsqueda bibliográfica en Medline, a través de PubMed, utilizando los términos Magnesium Sulfate, Pharmacology, Obstetrics, Pre-eclampsia, Eclampsia, Neuroprotective Agents. Se adicionaron otros artículos con el fin de ampliar información en ciertos temas. Conclusiones: Las propiedades farmacológicas que expresa el sulfato de magnesio se relacionan directamente con su efecto antagónico con el calcio. Muestra efectos a nivel muscular, neuronal, cardiovascular, entre otros. Sus usos en obstetricia abarcan principalmente el manejo de la preeclampsia, prevención de la eclampsia, y prevención de la parálisis cerebral del recién nacido prematuro. El uso como agente tocolítico en el trabajo de parto prematuro aun es discutido ya que la evidencia es inconclusa.

Introduction: Since its first use in 1926 in eclampsia´s management magnesium sulphate has been a drug used and studied extensively by obstetricians. For a long time, practitioners remained sceptical about its potential benefits but the emergence of well-structured studies provided evidence in favor and against. Objective: A review of the literature on the pharmacology, physiology, pharmacokinetics, mechanisms of action, main applications and schemes of administration of the sulfate of magnesium in obstetrics. Methodology: Search in the database MEDLINE via PubMed, using the terms: Magnesium Sulfate, pharmacology, Obstetrics, Preeclampsia, Eclampsia, Neuroprotective Agents. Other papers were added in order to expand information on some topics. Conclusions: The pharmacological properties that express the magnesium sulfate is linked directly with its effect antagonistic with the calcium. Shows effects to level muscle, neuronal, cardiovascular, among others. Its uses in obstetrics include mainly the management of preeclampsia, prevention of eclampsia, and prevention of cerebral palsy in the premature neonate. The magnesium sulphate tocolytic effects even is discussed because the evidence is inconclusive.

Introdução: Desde que o sulfato de magnésio foi utilizado em 1926, no tratamento de eclampsia, tem sido usado e amplamente estudado por obstetras. Longo o ceticismo sobre seus potenciais benefícios permaneceu, mas tarde o aparecimento de estudos bem estruturados forneceram evidências a favor ou contra algum destes. Objetivo: Revisar a literatura sobre a farmacologia, fisiologia, fármaco cinética, mecanismos de ação, principais usos e administração de sulfato de magnésio em obstetrícia. Metodologia: Pesquisa bibliográfica Medline via PubMed utilizando os termos sulfato de magnésio, farmacologia, obstetrícia, pré-eclâmpsia, eclâmpsia, agentes neuroprotectores. Foram adicionados outros itens, a fim de obter maior informação sobre determinados temas. Conclusões: As propriedades farmacológicas que expressa o sulfato de magnésio estão diretamente relacionadas com o efeito antagônico do cálcio. Mostra os efeitos a nível muscular, neuronal, cardiovascular, entre outros. Em obstetrícia o uso abrange principalmente o tratamento da pré-eclampsia, a prevenção da eclampsia, e prevenção de paralisia cerebral no recém-nascido prematuro. Usa-lo como agente toco lítico no trabalho de parto prematuro é incerto porque a evidência é inconclusa.

Uso do lítio no tratamento de Alzheimer / Use of lithium in Alzheimer's treatment

A doença de Alzheimer (DA) é a causa mais comum de demência em idosos. As principais lesões cerebrais encontradas nesses pacientes são placas neuríticas com depósitos extracelulares de proteína ß-amiloide e um emaranhado neurofibrilar localizado normalmente no citoplasma perinuclear e composto de proteínas Tau hiperfosforiladas. Nos estágios iniciais, nota-se deficiência da memória recente, lapsos de memória, confusão e queda no rendimento funcional em tarefas complexas. Apesar de todo o conhecimento de sua fisiopatogenia, ainda não foram descritas terapias completamente eficazes para seu tratamento, sendo que o tratamento de primeira escolha é feito com fármacos inibidores da colinesterase. Estudos sugerem que o tratamento crônico com lítio potencializa a sobrevivência de novas células induzida por enriquecimento ambiental no hipocampo, proporcionando um ambiente favorável para os estímulos ambientais exercerem um efeito protetor mais forte. Deste modo, o tratamento combinado com lítio e enriquecimento ambiental poderia constituir uma estratégia para promover a sobrevivência de novos neurônios e, assim, melhorar a função cognitiva na doença de Alzheimer, especialmente em estágio inicial.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The two major brain lesions found in patients with Alzheimer's disease are neuritic plaques, which contain extracellular deposits of amyloid ß-protein and neurofibrillary tangle typically located in the perinuclear cytoplasm and composed of hyperphosphorylated Tau protein. In the early stages, the patient has a deficiency of recent memory, tends to commit lapses and to blur easily, besides presenting drop in its functional performance in complex tasks. Despite all the knowledge about the pathogenesis of Alzheimer's disease, have not yet been described completely effective therapies for the treatment of disease and the first choice of treatment is done with cholinesterase inhibitor drugs. Studies suggest that chronic treatment with lithium enhances the survival of new cells induced by environmental enrichment in the hippocampus, providing an environment conducive to environmental stimuli exert a stronger protective effect. Thus, combined treatment with lithium and environmental enrichment could be a strategy to promote the survival of new neurons and thus improve cognitive function in Alzheimer's disease, particularly in the initial stage.

Neurotrophic factors in Parkinson's disease are regulated by exercise: Evidence-based practice.

We carried out a qualitative review of the literature on the influence of forced or voluntary exercise in Parkinson's Disease (PD)-induced animals, to better understand neural mechanisms and the role of neurotrophic factors (NFs) involved in the improvement of motor behavior. A few studies indicated that forced or voluntary exercise may promote neuroprotection, through upregulation of NF expression, against toxicity of drugs that simulate PD. Forced training, such as treadmill exercise and forced-limb use, adopted in most studies, in addition to voluntary exercise on a running wheel are suitable methods for NFs upregulation.

Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

OBJECTIVES : To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion. METHODS: Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared. RESULTS: Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups. CONCLUSION: Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats. .

The neuroprotective effect of Sulindac after ischemia-reperfusion injury in rats

To investigate the neuroprotective effects of Sulindac on the hippocampal complex after global cerebral ischemia/reperfusion (I/R) injury in rats. Thirty one Sprague-Dawley rats were used, distributed into group I (sham) n:7 were used as control. For group II (n:8), III (n:8) and IV (n:8) rats, cerebral ischemia was performed via the occlusion of bilateral internal carotid artery for 45 minutes and continued with reperfusion process. 0.3 mL/kg/h 0.9 % sodium chloride was infused intraperitoneally to the Group II rats before ischemia, 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group III rats before ischemia and 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group IV rats after ischemia and before reperfusion process. The levels of MDA, GSH and MPO activity were measured in the left hippocampus tissue. The hippocampal tissue of all group members were taken for histopathological study. The MDA and MPO levels increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). Beside these, the GSH levels decreased from group I (control) to group II (I/R) (P<0.05) and increased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05).The number of apoptotic neurons increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). The Sulindac may have neuroprotective effects on ischemic neural tissue to prevent the reperfusion injury after ischemia.(AU)

The neuroprotective effect of Sulindac after ischemia-reperfusion injury in rats

To investigate the neuroprotective effects of Sulindac on the hippocampal complex after global cerebral ischemia/reperfusion (I/R) injury in rats. Thirty one Sprague-Dawley rats were used, distributed into group I (sham) n:7 were used as control. For group II (n:8), III (n:8) and IV (n:8) rats, cerebral ischemia was performed via the occlusion of bilateral internal carotid artery for 45 minutes and continued with reperfusion process. 0.3 mL/kg/h 0.9 % sodium chloride was infused intraperitoneally to the Group II rats before ischemia, 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group III rats before ischemia and 5μg/kg/h/0.3 ml sulindac was infused intraperitoneally to the Group IV rats after ischemia and before reperfusion process. The levels of MDA, GSH and MPO activity were measured in the left hippocampus tissue. The hippocampal tissue of all group members were taken for histopathological study. The MDA and MPO levels increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). Beside these, the GSH levels decreased from group I (control) to group II (I/R) (P<0.05) and increased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05).The number of apoptotic neurons increased from group I (control) to group II (I/R) (P<0.05) and decreased from group II (I/R) to group III (presulindac + I/R) and IV (postsulindac + I/R) (P<0.05). The Sulindac may have neuroprotective effects on ischemic neural tissue to prevent the reperfusion injury after ischemia.

Fisiopatologia do Transtorno de Humor Bipolar e efeito do tratamento com lítio: enfoque em neuroproteção e função mitocondrial / Bipolar disorder pathophysiology and the effect of lithium treatment: focus on neuroprotection and mitochondrial function

Introdução: Diversas evidências apontam para um papel da disfunção mitocondrial no Transtorno de Humor Bipolar (THB), mas pouco se sabe sobre isso no THB de início recente. Na mitocôndria a atividade da cadeia transportadora de elétrons (CTE) atua juntamente com o ciclo do ácido cítrico na produção de energia, mas não está claro se estão alteradas no THB. O DNA mitocondrial (DNAmt) codifica diversas proteínas da CTE e está associado ao estresse oxidativo, mas nunca foi avaliado em pacientes no THB in vivo. O estresse oxidativo está associado ao THB e à disfunção mitocondrial, mas não se sabe muito das atividades das enzimas antioxidantes no THB de início recente. O óxido nítrico (NO) é uma molécula com efeitos neuromoduladores, mas com um papel no THB ainda não elucidado. O lítio é um tratamento padrão-ouro no THB, tendo mostrado efeitos neuroprotetores. Apesar disso, pouco se conhece do efeito do lítio na CTE, nas enzimas do ciclo do ácido cítrico, no conteúdo de DNAmt e na regulação de NO em humanos. Também não está claro o papel antioxidante do lítio no THB. Metódos: Pacientes com THB em depressão (n=31), não medicados em sua maioria (84%), foram tratados por 6 semanas com lítio. Antes e depois do tratamento, verificaram-se em leucócitos as atividades dos complexos I-IV da CTE, atividades das enzimas citrato sintase, succinato desidrogenase e malato desidrogenase e também o conteúdo de DNAmt; em plasma foram analisados os níveis de NO, substâncias reativas ao ácido tiobarbitúrico (TBARS) e as atividades de catalase (CAT), glutationa peroxidase (GPx), superóxido dismutase (SOD) e razão de SOD/CAT. Os pacientes com depressão bipolar foram comparados com 28 controles saudáveis. Resultados: Em comparação com controles, os pacientes com THB tiveram um aumento de GPx (p < 0,001) e CAT (p=0,005) e uma diminuição de SOD/CAT (p=0,001), sem outras diferenças nos demais biomarcadores. Pacientes com THB I mostraram uma diminuição de citrato sintase (p=0,02) e uma...

Background: Several evidences point to a role for mitochondrial dysfunction in Bipolar Disorder (BD), but few is known about it on short-term BD. In mitochondria the electron transport chain (ETC) acts jointly with citric acid cycle to produce energy, but it is not clear if they are altered in BD. Mitochondrial DNA (mtDNA) encodes several ETC proteins and is associated with oxidative stress, but it was never evaluated in BD in vivo. Oxidative stress is associated with BD and with mitochondrial dysfunction, but few is known about the activities of antioxidant enzymes in short-term BD. Nitric oxide (NO) is a molecule with neuromodulatory effects, but with an unclear role in BD. Lithium is a gold-standard treatment for BD, which has shown neuroprotective effects. However, few is known about lithium effect on ETC, citric acid cycle, mtDNA content, and NO regulation in humans. Also, lithium's antioxidant role in BD is unclear. Methods: Patients with BD depression (n=31) unmedicated in majority (84%) received lithium treatment for 6 weeks. Before and after treatment, in leukocytes the activities of ETC complex I-IV, citrate synthase, succinate dehydrogenase, and malate dehydrogenase, and mtDNA content were evaluated; in plasma, NO levels, thiobarbituric acid reactive substances (TBARS), the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and SOD/CAT ratio were evaluated. Bipolar depression patients were compared with 28 healthy controls. Results: When compared with controls, BD patients showed an increase in GPx (p < 0.001) and CAT (p=0.005) and a decrease in SOD/CAT (p=0.001), but showed no difference for other biomarkers. Patients with BD I showed a decrease in citrate synthase (p=0.02) and a slight decrease in mtDNA content (p=0.05) when compared to BD II; mtDNA content was slightly decreased in BD I compared to controls (p=0.05). From baseline to endpoint, there was an increase in ETC complex I activity (p=0.02),...

Cannabinoides y su posible uso en el glaucoma / Cannabinoids and their possible use in the treatment of glaucoma

Aunque la planta Cannabis sativa ha sido empleada desde la más remota antigüedad con fines medicinales, uno de sus derivados, la marihuana, se ha convertido en la droga de uso ilegal más consumida en el mundo. Asimismo tanto el Cannabis como sus cannabinoides se emplean como terapéutico en pocas enfermedades generalmente neurológicas. Se realizó una revisión bibliográfica para exponer el posible uso de los cannabinoides en la terapéutica del glaucoma. Para ello se tuvo en cuenta la literatura disponible sobre el tema, durante el período enero a septiembre de 2010. Se ha comprobado el efecto hipotensor ocular de los cannabinoides al disminuir la producción de humor acuoso, y aumentar la excreción de humor acuoso a través de la malla trabecular y la vía uveoescleral, efecto compatible con el hallazgo de elevadas concentraciones de receptores de cannabinoides rCB1 y rCB2; además, el tetrahidrocannabinol ha demostrado disminuir el efecto neurodegenerativo en modelos de isquemia cerebral en ratas y se evidenció también el efecto beneficioso de los cannabinoides al disminuir la degeneración secundaria asociada al glaucoma mediada por la excitotoxicidad del glutamato. Estos hallazgos sobre el efecto beneficioso de los cannabinoides como hipotensores oculares y por su efecto neuroprotector, transmiten un mensaje esperanzador sobre la función que estos podrían desempeñar en el campo del glaucoma, aunque para mayor seguridad y eficacia serían necesarios ensayos clínicos encaminados a valorar su aplicabilidad en la práctica clínica diaria

Although the Cannabis Sativa plant has been used since the most remote ancient times for medicinal purposes, one of its derivatives, marijuana, has become the most commonly used illegal drug in the world. Similarly, both Cannabis and the cannabinoids are used therapeutically in a small number of general neurological pathologies. Literature review was made to set forth the possible use of cannabinoids in the treatment of Glaucoma. To this end, t the available literature on the subject from January to September 2010 was taken into account. The cannabinoid´s antihypertensive occular effect has been found to decrease aqueous humor production, and to increase the excretion of aqueous humor through the trabeculary mesh and the route uveoscleral pathway. This effect is compatible with the high concentrations of rCB1 and rCB2 cannabinoid receptors found. Besides, tetrahydrocannabinol has proved to reduce the neurodegenerative effect in models of cerebral ischemia in rats and the beneficial effect of cannabinoids to reduce gluthamate excitotoxicity-mediated secondary degeneration associated with glaucoma. These findings about the beneficial effect of cannabinoids as ocular antihypertensives and its neuroprotective effect convey a hopeful message about the role they could play in the treatment of glaucoma; however, it would be necessary to perform further clinical trials to assess their applicability in our daily clinical practice for greater safety and efficiency