Search

Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjogren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed. info:eu-repo/semantics/publishedVersion

Parkinson’s disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson’s disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.

Background:Dapsone (4,4'-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death.Objective:To provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials.Methods:We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death.Conclusion:The evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

Amphibians and reptiles are important indicators of ecosystem health, yet their populations are declining worldwide due to habitat loss and climate change. Agroecosystems, such as coffee plantations, can provide important habitat for these species. We conducted field surveys in the Sumapaz region of Colombia to identify the microclimatic variables that influence the diversity and abundance of herpetofauna in coffee crops. The canonical correspondence analysis revealed that leaf litter abundance, crop area, and age category were the most important structural variables for determining herpetofauna diversity. Our findings suggest that coffee plantations function similarly to secondary vegetation, and maintaining a thick layer of leaf litter is critical for establishing complex and structured animal communities. This study proposes a set of sustainable agricultural management principles to promote the existence of amphibians and reptiles in coffee crops. By adopting these practices, it is possible to prevent the decline in the population of amphibians and reptiles due to the expansion of the agricultural frontier, as seen in other coffee-growing regions. The findings of this study contribute to a better understanding of how to balance agricultural production and biodiversity conservation in the context of agroecosystems.*Una versión en español de este documento puede ser encontrada como material suplementario/ a Spanish version of this paper can be found as supplementary material.

Parkinson’s disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin or tween-80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four h and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin reduced significantly the MPP+-induced damage compared to MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson’s disease, and since there is not currently a proteomic map of the Nigro striatum of rats, and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation are decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and for the first time the molecular mechanisms involved in this protective effect.

Este libro es el primero de tres que se editan en el marco del programa Colombia Científica-Alianza efi en su componente macroeconómico. En este compendio de trabajos, el lector encontrará reflexiones críticas, formales y sistemáticas sobre temas significativos para el estudio de la informalidad, como su medición, aspectos macroeconómicos de su modelación, calidad del empleo, sus vínculos con la institucionalidad, y se avanza en el análisis de su relación con el crecimiento y desarrollo económicos, aproximándose a los choques externos. Este esfuerzo del conjunto de autores que aquí han contribuido es el fruto de la creación de un ecosistema de universidades y de un grupo crítico de investigadores preocupados por este fenómeno de las economías modernas, que tiene tanto de fascinante como de preocupante.

Introduction A first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes. Objective To determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI. Methods Twenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements. Results According to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group. Conclusions Patients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α

Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity. The cytoprotective effect of metallothionein (MT), a protein with high capacity to chelate metals, at two doses (100 and 600 µg/rat), was tested. Prussian blue (PB) (50 mg/kg) was administered alone or in combination with MT. A dose of Tl (16mg/kg) was injected i.p. to Wistar rats. Antidotes were administered twice daily, starting 24h after Tl injection, for 4 days. Tl concentrations diminished in most organs (p

3,4-Dihydroxyphenyl ethanol, known as hydroxytyrosol (HTy), is a phenylpropanoid found in diverse vegetable species. Several studies have demonstrated that HTy is a potent antioxidant. Thus, our study is aimed to evaluate the antioxidant effect of HTy and its derivatives, hydroxytyrosol acetate (HTyA) and nitrohydroxytyrosol (HTyN), in a model of oxidative stress induced by 1-methyl-4-phenylpyridinium (MPP+) in rats. Rats were administered intravenously (i.v.) in the tail with 1 mL saline solution or polyphenol compound (1.5 mg/kg) 5 min before intrastriatal infusion of 10 µg MPP+/8 µL. We found that rats injured with MPP+, pretreatment with HTy, HTyA or HTyN significantly decreased ipsilateral turns. This result was consistent with a significant preservation of striatal dopamine levels and decreased lipid fluorescence products (LFP), a marker of oxidative stress. Brain GSH/GSSG ratio, from rats pretreated with HTy or HTyN showed a significant preservation of that marker, decreased as a consequence of MPP+-induced oxidative damage. These results show an antioxidant effect of HTy, HTyA and HTyN in the MPP+ model of Parkinson’s disease in the rat.

Background Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI. Methods To produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25-50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue. Results Acute treatment with amantadine reduced nociceptive behaviour. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine. Conclusions Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N-methyl-D-aspartate receptors activation. Significance This study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dose-dependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain. However, further research is required to provide evidence of the effectiveness and feasibility.

Neurodegenerative disorders have been linked to the decrease of copper concentrations in different regions of the brain. Therefore, intake of micronutrient supplements could be a therapeutic alternative. Since the copper distribution profile has not been elucidated yet, the aim of this study was to characterize and to analyze the concentration profile of a single administration of copper gluconate to rats by two routes of administration. Male Wistar rats were divided into three groups. The control group received vehicle (n = 5), and the experimental groups received 79.5 mg/kg of copper orally (n = 4-6) or 0.64 mg/kg of copper intravenously. (n = 3-4). Blood, striatum, midbrain and liver samples were collected at different times. Copper concentrations were assessed using atomic absorption spectrophotometry. Copper concentration in samples from the control group were considered as baseline. The highest copper concentration in plasma was observed at 1.5 h after oral administration, while copper was quickly compartmentalized within the first hour after intravenous administration. The striatum evidenced a maximum metal concentration at 0.25 h for both routes of administration, however, the midbrain did not show any change. The highest concentration of the metal was held by the liver. The use of copper salts as replacement therapy should consider its rapid and discrete accumulation into the brain and the rapid and massive distribution of the metal into the liver for both oral and intravenous routes. Development of controlled-release pharmaceutical formulations may overcome the problems that the liver accumulation may imply, particularly, for hepatic copper toxicity.

Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [PET data evaluated at 2 h showed hyper-uptake of [This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.

Drug-resistant epilepsy is defined as “the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules”, 30-40% of the patients with epilepsy present this condition decreasing their quality-of-life and increasing mortality risk. Current literature suggests therapeutic alternatives such as surgery or neurostimulation, but they show some limitations. Unless degenerative progression is prevented and the regulatory role of interneurons is restored, patients with drug-resistant epilepsy may not reach seizure freedom. Ongoing studies have developed techniques to manoeuvre signalling pathways for neural regeneration in the central nervous system, this is defined as “the regrowth or repair of nervous tissues, cells or cell products”. This scoping review protocol aims to evaluate the therapeutic potential of modulating nerve regeneration pathways for patients with drug-resistant epilepsy. Published studies (all publication types) will be retrieved from Web of Science, PubMed, Scopus, EBSCOhost, Ovid, and Google Scholar, from database inception to present. Studies describing patients or experimental models of drug-resistant epilepsy receiving any treatment modulating nerve regeneration pathways will be included. Studies in languages different than Spanish or English that could not be appropriately translated or whose full-text files could not be retrieved after all efforts made will be excluded. Studies will be assessed for eligibility by two independent researchers. Results will be presented in tables. A narrative synthesis will be provided.

Lead (Pb), mercury (Hg), and manganese (Mn) are neurotoxic, but little is known about the neurodevelopmental effects associated with simultaneous prenatal exposure to these metals. We aimed to study the associations of Pb, Hg, and Mn prenatal levels (jointly and separately) with neurodevelopment in the first year of life. Methods: Pb, Hg, and Mn blood lead levels were measured in 253 pregnant women. Their offspring’s neurodevelopment was assessed through the Bayley Scale of Infant Development III® at one, three, six, and twelve months. The metals’ mean blood levels (µg/L) were Pb = 11.2, Hg = 2.1, and Mn = 10.2. Mean language, cognitive, and motor development scores of the infants at each age were between low-average and average. Multilevel models’ results showed that language development coefficients of the offspring decreased by 1.5 points per 1 µg/dL increase in maternal blood lead levels (p = 0.002); the magnitude of the aforementioned association increased in children with maternal blood Mn < 9.6 µg/L (ß = −1.9, p = 0.003) or Hg > 1.9 µg/L (ß = −1.6, p = 0.013). Cognitive and motor development had negative associations with maternal blood Pb levels; the latter was statistically significant when the interaction term between Pb, Mn, and Hg was included (ß = −0.037, p = 0.03). Prenatal exposure to low Pb levels may impair infants’ neurodevelopment in the first year of life, even more so if they are exposed to Hg or deficient in Mn.

Background Excessive occlusal forces and occlusal trauma have been implicated as co-destructive factors for periodontitis in animal models. The objective of this study was to assess the association between occlusal trauma and periodontitis. Methods A total of 167 cases and 205 controls were included for analysis. Occlusal trauma was the exposures of interest and was registered for cases and controls. Additional clinical co-variables were registered as well for further analysis. The association of the exposure and periodontitis was determined by the odds ratio and logistic regression analysis adjusted for confounders. Results Amalgam restorations, pathogenic occlusion and occlusal trauma were more frequent in cases as compared to controls (P ≤ 0.05). The distribution of pathogenic occlusion and occlusal trauma was similar according to the stage and class of periodontitis. Logistic regression analysis showed a significant association for cigarette smoking, systemic conditions, amalgam restorations, pathogenic occlusion, and occlusal trauma with periodontitis (P ≤ 0.05). After adjusting for confounding variables in the model, amalgam restorations and occlusal trauma remained strongly associated with periodontitis (P ≤ 0.05). Conclusions Occlusal trauma is strongly associated with periodontitis. Additional long-term prospective studies are necessary to further understand the impact of the occlusal condition and periodontitis.

Puberty is a transitional period from juvenile stage to adulthood, followed by the functional maturation of gonads and reproductive organs. This period is sensitive to environmental pollutants like cadmium (Cd), a heavy metal that represents a serious health risk. Cd is an endocrine disruptor that interferes with reproduction by causing oxidative stress in the reproductive organs, affecting the sexual function and decreasing testosterone (T) levels. However, little research has been done on the effects of Cd on puberty markers and antioxidant systems. In this study, we evaluated the effects of Cd on puberty markers: preputial separation, testes descent and T levels, and the antioxidant activity (SOD, CAT, GSH/GSSG and TAC) in the seminal vesicles, testis and epididymis. Male Wistar pups were treated with 1 mg/kg Cd or saline solution by i.p. injection from day 1 to 35; the other treatment was administrated for 49 days. At the end of treatment, the animals were sacrificed, and the tissues of interest dissected, weighed and prepared for the respective assays. Cd treated rats from birth to puberty showed a delay onset in the puberty markers and a low weight in reproductive organs. Also, Cd induced differential effects on the redox system in reproductive organs and decreased T levels, these effects played a pivotal role in the delay of puberty markers onset (testes descent and preputial separation), affecting the development and sexual maturity of the male rats.

Antecedentes: México es uno de los países Latinoamericanos con mayor productividad científica. Una de las publicaciones mexicanas con mayor continuidad es Archivos de Neurociencias (Arch Neurocien). Arch Neurocien evalúa su desempeño mediante indicadores basados en el conteo de las citas que reciben sus artículos. Uno de los más difundidos es el "Factor de Impacto™” (FI). El FI mide el número promedio de citas de los artículos publicados en las revistas indizadas en el Journal of Citation Reports (JCR). Existen otros indicadores similares, como CiteScore y Scimago Journal Rank (SJR). Entre ellos, el FI representa el “estándar de oro”. Arch Neurocien no se encuentra indizada en el JCR. Objetivo: En el presente estudio, se calculó un Factor de Impacto Estimado (FIE) para la Revista. Método: Se utilizó la metodología de Clarivate Analytics. Los resultados se compararon con otros dos indicadores para definir un diagnóstico cuantitativo del impacto científico de la revista. Resultados: Arch Neurocien registró un promedio de 0.39 citas/artículo. La revista en la que más se cita a Arch Neurocien fue la propia revista (autocitas), seguida por la Revista de Neurología (España) y la Revista Mexicana de Neurociencias. El FIE promedio fue 0.027±0.005. El mayor FIE correspondió al año 2001 con 0.068. El FIE correlacionó significativamente con CiteScore (r=0.916, r2=0.840, p=0.010) y SJR (r=0.736, r2=0.543, p=0.001). Conclusión: Se sugieren algunas estrategias para aumentar la calidad de los artículos publicados como realizar una reingeniería del comité editorial, promover el acceso abierto de las publicaciones, e impulsar estrategias para su difusión masiva.

La Deshidroepiandrosterona (DHEA) no solo es un esteroide activo por sí mismo, sino que también genera efectos independientes de receptores nucleares. Paulatinamente, se han obtenido más hallazgos sobre la síntesis de esteroides en el Sistema Nervioso Central (SNC), observándose que las diferencias con los tejidos endócrinos son menores. Es quizás en esas vías donde se podría encontrar la explicación de los múltiples efectos que puede causar un solo compuesto como la DHEA. Tan solo en el SNC, algunas de sus acciones incluyen neuroprotección, crecimiento de dendritas, apoptosis, síntesis y secreción de catecolaminas, así como funciones antioxidantes, anti-inflamatorias y anti­glucocorticoides. Las variaciones en la concentración sérica de la DHEA se asocian con diversas enfermedades. Esta concentración disminuye con la edad desde su máximo en la juventud hasta su punto más bajo, cuando muchos trastornos del envejecimiento se vuelven notablemente más frecuentes. Tanto la DHEA como sus congéneres pueden actuar por sí mismos o ser metabolizados a otros compuestos activos, aumentando así la complejidad de sus efectos. Por tales motivos, cobra relevancia describir dichas interacciones metabólicas para mejorar la interpretación de los estudios de estos mensajeros.

Heavy metals (HM) can be accumulated along the food chain; their presence in food is a global concern for human health because some of them are toxic even at low concentrations. Unprocessed or minimally processed foods are good sources of different nutrients, so their safety and quality composition should be guaranteed in the most natural form that is obtained for human consumption. The objective of this scoping review (ScR) is to summarize the existing evidence about the presence of HM content (arsenic (As), lead (Pb), cadmium (Cd), mercury (Hg), methylmercury (MeHg), and aluminum (Al)) in unprocessed or minimally processed foods for human consumption worldwide during the period of 2011–2020. As a second objective, we identified reported HM values in food with respect to Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) International Food Standards for Maximum Limits (MLs) for contaminants in food. This ScR was conducted in accordance with the Joanna Briggs Institute (JBI) methodology and PRISMA Extension for Scoping Reviews (PRISMA-ScR); advance searches were performed in PubMed, ScienceDirect and FAO AGRIS (Agricultural Science and Technology Information) databases by two reviewers who independently performed literature searches with specific eligibility criteria. We classified individual foods in food groups and subgroups according to the Global Individual Information Food Consumption Data Tool (FAO/WHO GIFT). We homologated all the reported HM units to parts per million (ppm) to determine the weighted mean HM concentration per country and food group/subgroup of the articles included. Then, we compared HM concentration findings with FAO/WHO MLs. Finally, we used a Geographic Information System (GIS) to present our findings. Using our search strategy, we included 152 articles. Asia was the continent with the highest number of publications (n = 79, 51.3%), with China being the country with the largest number of studies (n = 34). Fish and shellfish (n = 58), followed by vegetables (n = 39) and cereals (n = 38), were the food groups studied the most. Fish (n = 42), rice (n = 33), and leafy (n = 28) and fruiting vegetables (n = 29) were the most studied food subgroups. With respect to the HM of interest, Cd was the most analyzed, followed by Pb, As, Hg and Al. Finally, we found that many of the HM concentrations reported exceeded the FAO/OMS MLs established for Cd, Pb and As globally in all food groups, mainly in vegetables, followed by the roots and tubers, and cereals food groups. Our study highlights the presence of HM in the most natural forms of food around the world, in concentrations that, in fact, exceed the MLs, which affects food safety and could represent a human health risk. In countries with regulations on these topics, a monitoring system is recommended to evaluate and monitor compliance with national standards. For countries without a regulation system, it is recommended to adopt international guidelines, such as those of FAO, and implement a monitoring system that supervises national compliance. In both cases, the information must be disseminated to the population to create social awareness. This is especially important to protect the population from the consumption of internal production and for the international markets of the globalized world.

Introduction: Each year, approximately 795,000 people experience a new or recurrent stroke, either ischemic or hemorrhagic. The current therapeutical approach for acute ischemic stroke includes thrombolysis and mechanical thrombectomy; still, no neuroprotective treatment options currently exist to improve its neurological outcome. Some components of the endocannabinoid system are altered after ischemic stroke. It is considered that cannabinoids may exert neuroprotective effects; however, the use of cannabinoid receptor ligands is a major concern due to its psychotropic properties. Regardless that there are many studies describing the benefit of administering cannabinoids for experimental stroke several unanswered questions remain since most of the information point up in non-human species. A previous systematic review detected significant heterogeneity among studies, so it is appropriate to perform a scoping review to evaluate the feasibility of performing an updated systematic review and meta-analysis. This scoping review aims to evaluate the therapeutic potential of modulating the endocannabinoid system for stroke. Methods: Published studies (all publication types) will be retrieved from Web of Science, PubMed, Scopus, Ovid, EBSCOhost, and Google Scholar. Eligibility criteria: Clinical or preclinical studies reporting endocannabinoid levels or their effects, or reporting administration of cannabinoid modulators (stimulating or inhibiting their synthesis or metabolism, phytocannabinoids, or synthetic cannabinoids), in patients or models of stroke will be considered for inclusion. Studies written in languages different than Spanish or English that could not be appropriately translated, or whose full-text files could not be retrieved will be excluded. Data charting: Results will be summarized in tabular form. This protocol complies with PRISMA-P.

Introduction: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver disease and/or portosystemic blood shunting, characterized by alterations of alertness, personality, cognition, and motor functions. Its severity is defined from mild symptoms to coma according to four grades. This disease may affect several brain regions including the cingulate gyrus, the insular cortex, and the globus pallidus. The pathophysiology of HE is thought to be multifactorial and involves manganese accumulation in the brain, damaging effect of ammonia on glial cells, etc. Previous studies describe the pathophysiology of HE or the effect of manganese in the central nervous system but there is no review addressing both topics from an integrative perspective and using a systematic methodology. This scoping review aims to evaluate the role of manganese in HE. Methods: Published studies (all publication types) will be retrieved from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid, and Google Scholar. Inclusion criteria are: studies reporting manganese levels in any biological sample or tissue of patients with HE, any experimental model reporting the effect of manganese administration on measures of neuroprotection in models of liver damage, or showing an effect on manganese levels in the liver and/or the brain. Exclusion criteria are: studies reporting subjects exposed occupationally or environmentally to manganese, or written in languages different than Spanish or English that could not be appropriately translated, or whose full-text files could not be retrieved. Either clinical or preclinical studies will be analyzed separately but might be discussed together. Data summaries will be presented in graphs, figures, and tables. A narrative synthesis will be presented. This protocol complies with PRISMA-P.