Hasil untuk "Neurosciences. Biological psychiatry. Neuropsychiatry"

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DOAJ Open Access 2025
Responsiveness of European countries to the population mental health needs: A cross-national comparison study

Celso Arango, Andrea Fiorillo, Geert Dom et al.

Abstract Background This study aimed to cross-compare European countries’ responsiveness to their populations’ mental health (MH) needs. Methods For the EU-27 countries and the United Kingdom, the 2023 Headway Initiative collected data on 15 key performance indicators (KPIs) in responsiveness in healthcare, including workforce, facilities, quality of care, and MH expenditure, and 14 KPIs in responsiveness in workplaces, schools, and society. Bivariate correlations between Headway-transformed KPI scores, which were standardised in a 1–10 Likert Scale (1: worst performance; 10: best performance), tested for putative associations. Results Responsiveness in healthcare: Sweden (10), Denmark (8.8), and Finland (8.3) showed the best performance, while Romania (1.0), Slovakia (1.1), and Latvia and Bulgaria (1.2) had the poorest performance. Responsiveness in workplaces: schools, and society, Germany (10.0), France (9.1), and Denmark (9.1) were the most responsive countries, while Greece and Slovakia (1.0) had the poorest responsiveness. MH status total scores negatively correlated with global scores on responsiveness in healthcare (r = −0.34, p = .075), workplaces (r = −0.46, p = .014), schools (r = −0.59, p = .003), and society (r = −0.53, p = .003) – poorer MH status, greater responsiveness. Conclusions European countries significantly differed in their responsiveness to the populations’ MH needs, although the real effectiveness of their MH policies remains to be elucidated. Whether more responsive countries, which achieved poorer MH outcomes, successfully met greater preexisting MH needs, they failed to do so, or the relationship is driven by other third variables (e.g., quality of MH assessment) requires future investigation.

DOAJ Open Access 2025
The Moderating Role of Willpower as a Personality Trait in the Relationship Between Social Influence and Moral Disengagement Contradiction

Nesrullah Okan

Abstract Objective: The objective of this study is to examine the moderating role of willpower, conceptualized as a personality trait, in the relationship between social influence and moral disengagement towards migrants. The mediating role of spiritual contradiction is also investigated to understand the interplay between individual traits, moral contradictions, and external social pressures. Method: Data were collected from 720 participants using validated self‐report measures. Structural equation modeling (SEM) was employed to test the proposed relationships among social influence, moral disengagement, spiritual contradiction, and willpower. Moderation and mediation analyses were conducted to evaluate the hypothesized model. Results: The findings reveal that social influence significantly predicts moral disengagement. This relationship is partially mediated by spiritual contradiction, which amplifies disengagement by reflecting tensions between internal moral values and external norms. In addition, the study found that willpower moderates this relationship by reducing the negative impact of social influence on moral disengagement. Individuals with higher levels of willpower demonstrate greater resistance to moral disengagement and maintain moral consistency despite external pressures and moral contradictions. Conclusions: This study underlines the pivotal function of personality traits and spiritual dimensions in shaping moral processes. The findings have practical applications for ethical education and interventions designed to enhance moral resilience in varied social contexts.

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2025
TIME: Tractography-Informed myelin estimation

Sara Bosticardo, Matteo Battocchio, Mario Ocampo-Pineda et al.

Investigating myelin integrity within multiple sclerosis (MS) lesions and in normal-appearing white matter is crucial for understanding demyelination and remyelination processes. While most approaches assess global myelin changes or compare lesions with homologous regions in healthy controls, they do not allow direct within-tract comparisons between lesional and non-lesional tissue.We introduce the tractography-informed myelin estimate (TIME), a novel map designed to quantify tract-specific myelin loss. TIME integrates tractography with myelin-sensitive imaging, such as myelin volume fraction, to compare lesional and non-lesional segments within the same white matter tract. By modeling local deviations from the expected myelin volume fraction signal along streamlines, TIME captures tract-specific myelin damage while accounting for within-tract variability. TIME is based on a microstructure-informed tractography framework, with an extra compartment to model signal loss caused by lesions.We evaluated TIME in 159 MS patients, assessing its association with neurological disability at baseline and longitudinally over a median follow-up of two years. At baseline, higher myelin loss captured by TIME was significantly associated with worse disability (β = 0.14, p = 0.015). Longitudinally, greater baseline disability predicted faster TIME-quantified myelin loss, which was in turn associated with a higher risk of disability worsening. In contrast, lesion-averaged myelin volume fraction showed no significant associations with either baseline disability or its progression.TIME provides a detailed, tract-specific assessment of myelin damage, providing greater sensitivity than conventional metrics, highlighting its potential as a biomarker in MS.

Computer applications to medicine. Medical informatics, Neurology. Diseases of the nervous system
DOAJ Open Access 2025
A case series of Sneddon syndrome: clinical features, diagnostic workup, and literature review

Bruno Henrique Carneiro Costa Filho, Victor Ting Po Chy, João Augusto de Macedo Cavalcanti de Albuquerque et al.

Abstract Background Sneddon syndrome, a rare, non-inflammatory thrombotic vasculopathy characterized by livedo racemosa and cerebrovascular disease. Case presentation We present a case series of six women diagnosed with Sneddon syndrome. We conducted a thorough analysis of clinical, radiological, and laboratory data, including results of prothrombotic and autoimmune screening. Our findings emphasize the importance of considering Sneddon syndrome as a potential cause of stroke, particularly in young women, and underscore the necessity of a comprehensive dermatological examination when evaluating stroke etiology. Additionally, we provide a comprehensive literature review of the clinical manifestations, radiological and histopathological findings, as well as treatment options. Conclusion A thorough dermatological examination can aid in early detection of Sneddon syndrome and may change the course of treatment of stroke in young adults.

Neurology. Diseases of the nervous system
DOAJ Open Access 2024
Artificial Intelligence in Wound Care: A Narrative Review of the Currently Available Mobile Apps for Automatic Ulcer Segmentation

Davide Griffa, Alessio Natale, Yuri Merli et al.

<b>Introduction:</b> Chronic ulcers significantly burden healthcare systems, requiring precise measurement and assessment for effective treatment. Traditional methods, such as manual segmentation, are time-consuming and error-prone. This review evaluates the potential of artificial intelligence AI-powered mobile apps for automated ulcer segmentation and their application in clinical settings. <b>Methods:</b> A comprehensive literature search was conducted across PubMed, CINAHL, Cochrane, and Google Scholar databases. The review focused on mobile apps that use fully automatic AI algorithms for wound segmentation. Apps requiring additional hardware or needing more technical documentation were excluded. Vital technological features, clinical validation, and usability were analysed. <b>Results:</b> Ten mobile apps were identified, showing varying levels of segmentation accuracy and clinical validation. However, many apps did not publish sufficient information on the segmentation methods or algorithms used, and most lacked details on the databases employed for training their AI models. Additionally, several apps were unavailable in public repositories, limiting their accessibility and independent evaluation. These factors challenge their integration into clinical practice despite promising preliminary results. <b>Discussion:</b> AI-powered mobile apps offer significant potential for improving wound care by enhancing diagnostic accuracy and reducing the burden on healthcare professionals. Nonetheless, the lack of transparency regarding segmentation techniques, unpublished databases, and the limited availability of many apps in public repositories remain substantial barriers to widespread clinical adoption. <b>Conclusions:</b> AI-driven mobile apps for ulcer segmentation could revolutionise chronic wound management. However, overcoming limitations related to transparency, data availability, and accessibility is essential for their successful integration into healthcare systems.

Neurosciences. Biological psychiatry. Neuropsychiatry, Computer applications to medicine. Medical informatics
DOAJ Open Access 2024
Efficacy of non-pharmacological interventions on sleep quality in patients with cancer-related insomnia: a network meta-analysis

Yu Luo, Hua He, Caihong Cao et al.

ObjectiveDespite the widespread application of non-pharmacological therapies in treating cancer-related insomnia, a comprehensive assessment of these methods is lacking. This study aims to compare the efficacy of 11 non-pharmacological interventions for cancer-related insomnia, providing a theoretical basis for clinicians in choosing treatment methods.MethodsWe searched five databases, including the Cochrane Central Register of Controlled Trials, PubMed, Embase, Wiley Library, and Web of Science, for relevant randomized controlled trials. Included studies involved patients diagnosed with cancer-related insomnia, employed non-pharmacological treatments, and reported outcomes using the PSQI and ISI. Bayesian statistical methods were used for the network meta-analysis, and statistical processing was performed using Review Manager 5.4 and Stata 14.0 software. The results were thoroughly analyzed and evaluated, and publication bias was assessed using funnel plot tests.ResultsOur study included 41 randomized controlled trials, comprising 11 different non-pharmacological interventions (3,541 participants), the network analysis identifying Electroacupuncture as the most effective, with a SUCRA value of 92.2% in ISI, this was followed by Professionally administered Cognitive behavioral therapy for insomnia(PCBT-I) and Mindfulness-based cognitive therapy(MBCT), with SUCRA values of 78.4 and 64.1%, respectively. Traditional Cognitive behavioral therapy for insomnia(CBT-I) and VCBT-I showed lower efficacy with SUCRA values of 55.9 and 55.2%, respectively. Exercise interventions and control groups had the lowest efficacy, with SUCRA values of 24.0 and 16.1%. Using PSQI as the outcome measure, Massage therapy ranked highest in improving sleep quality with a SUCRA value of 92.2%, followed by Professionally administered Cognitive behavioral therapy for insomnia (PCBT-I) and Electroacupuncture. League tables indicated significant improvements in sleep outcomes for Electroacupuncture and MT compared to control groups, with Electroacupuncture (EA) showing an MD of −7.80 (95% CI: −14.45, −1.15) and MT an MD of −4.23 (CI: −8.00, −0.46).ConclusionConsidering both outcome indicators, Electroacupuncture was significantly effective in alleviating the severity of insomnia, while MT was most effective in improving sleep quality. Therefore, in the non-pharmacological interventions for cancer-related insomnia, Electroacupuncture and MT May be particularly effective choices. Future research should further explore the specific mechanisms of action of these interventions and their efficacy in different patient groups.

Neurology. Diseases of the nervous system
DOAJ Open Access 2023
An investigation of the association between focal damage and global network properties in cognitively impaired and cognitively preserved patients with multiple sclerosis

A. L. Wenger, A. L. Wenger, A. L. Wenger et al.

IntroductionThe presence of focal cortical and white matter damage in patients with multiple sclerosis (pwMS) might lead to specific alterations in brain networks that are associated with cognitive impairment. We applied microstructure-weighted connectomes to investigate (i) the relationship between global network metrics and information processing speed in pwMS, and (ii) whether the disruption provoked by focal lesions on global network metrics is associated to patients’ information processing speed.Materials and methodsSixty-eight pwMS and 92 healthy controls (HC) underwent neuropsychological examination and 3T brain MRI including multishell diffusion (dMRI), 3D FLAIR, and MP2RAGE. Whole-brain deterministic tractography and connectometry were performed on dMRI. Connectomes were obtained using the Spherical Mean Technique and were weighted for the intracellular fraction. We identified white matter lesions and cortical lesions on 3D FLAIR and MP2RAGE images, respectively. PwMS were subdivided into cognitively preserved (CPMS) and cognitively impaired (CIMS) using the Symbol Digit Modalities Test (SDMT) z-score at cut-off value of −1.5 standard deviations. Statistical analyses were performed using robust linear models with age, gender, and years of education as covariates, followed by correction for multiple testing.ResultsOut of 68 pwMS, 18 were CIMS and 50 were CPMS. We found significant changes in all global network metrics in pwMS vs HC (p &lt; 0.05), except for modularity. All global network metrics were positively correlated with SDMT, except for modularity which showed an inverse correlation. Cortical, leukocortical, and periventricular lesion volumes significantly influenced the relationship between (i) network density and information processing speed and (ii) modularity and information processing speed in pwMS. Interestingly, this was not the case, when an exploratory analysis was performed in the subgroup of CIMS patients.DiscussionOur study showed that cortical (especially leukocortical) and periventricular lesions affect the relationship between global network metrics and information processing speed in pwMS. Our data also suggest that in CIMS patients increased focal cortical and periventricular damage does not linearly affect the relationship between network properties and SDMT, suggesting that other mechanisms (e.g. disruption of local networks, loss of compensatory processes) might be responsible for the development of processing speed deficits.

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2023
The expansion of newborn neurons in hippocampus improves social recognition deficit in a mouse model of autism

Hu Meng, Qiongwei Li, Jinxin Wang et al.

IntroductionAutism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by core symptoms of impaired social interaction and communication. The pathological mechanism and treatment are not clear and need further study. Our previous study found that the deletion of high-risk gene Autism Susceptibility 2 (AUTS2) in mice led to dentate gyrus (DG) hypoplasia that highly associated with impaired social novelty recognition. Here we aim to improve the social deficit through increasing the neurogenesis in the subgranular zone (SGZ) and expanding the newborn granule neurons in DG.MethodsThree approaches including repeated oxytocin administration, feeding in enriched environment and overexpression of cyclin-dependent kinase 4 (Cdk4)-CyclinD1 complex in DG neural stem cells (NSCs) at the post-weaning stage were conducted.ResultsWe found that the number of EdU labeled proliferative NSCs or retrovirus labeled newborn neurons was significantly increased after manipulations. The social recognition deficit was also significantly improved.DiscussionOur findings suggested a possible strategy to restore the social deficit through expansion of newborn neurons in hippocampus, which might provide a new insight into the treatment of autism.

DOAJ Open Access 2022
The Role of Cerebrospinal Fluid Biomarkers in Dementia and Other Related Neurodegenerative Disorders

George P. Paraskevas

Over the course of the last 20 years, cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD), including amyloid beta peptide with 42 amino acids (Aβ<sub>42</sub>), total tau protein (τ<sub>T</sub>), and tau protein phosphorylated at a threonine residue at position 181 (τ<sub>P-181</sub>), have become a useful tool for the recognition and diagnosis of AD, even in early or atypical clinical presentations and in the presymptomatic stage of the disease [...]

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2022
Physician suicide demographics and the COVID-19 pandemic

Dante Duarte, Mirret M. El-Hagrassy, Tiago Couto et al.

Objective: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. Methods: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. Results: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). Conclusions: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

DOAJ Open Access 2022
Admission Random Blood Glucose, Fasting Blood Glucose, Stress Hyperglycemia Ratio, and Functional Outcomes in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis

Guangyong Chen, Junli Ren, Honghao Huang et al.

BackgroundStress hyperglycemia ratio (SHR), calculated as glucose/glycated hemoglobin, has recently been developed for assessing stress hyperglycemia and could provide prognostic information for various diseases. However, calculating SHR using random blood glucose (RBG) drawn on admission or fasting blood glucose (FBG) could lead to different results. This study intends to evaluate the association between SHR and functional outcomes in patients with acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (r-tPA) intravenous thrombolysis.MethodsData from 230 patients with AIS following thrombolytic therapy with r-tPA in the Third Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2019 were retrospectively reviewed. SHR1 was defined as [RBG (mmol/L)]/[HbA1c (%)] and SHR2 was defined as [FBG (mmol/L)]/[HbA1c (%)]. The outcomes included early neurological improvement (ENI), poor function defined as a modified Rankin Scale score (mRS) of 3–6, and all-cause death in 3 months. Multivariable logistic regression was performed to estimate the association between SHR and adverse outcomes.ResultsAfter adjustment for possible confounders, though patients with AIS with higher SHR1 tend to have a higher risk of poor outcome and death and unlikely to develop ENI, these did not reach the statistical significance. In contrast, SHR2 was independently associated with poor functional outcome (per 0.1-point increases: odds ratios (OR) = 1.383 95% CI [1.147–1.668]). Further adjusted for body mass index (BMI), triglyceride-glucose index (TyG), and diabetes slightly strengthen the association between SHR (both 1 and 2) and adverse outcomes. In subgroup analysis, elevated SHR1 is associated with poor functional outcomes (per 0.1-point increases: OR = 1.246 95% CI [1.041–1.492]) in non-diabetic individuals and the association between SHR2 and the poor outcomes was attenuated in non-cardioembolic AIS.ConclusionSHR is expected to replace random or fasting glucose concentration as a novel generation of prognostic indicator and a potential therapeutic target.

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2021
Annexin A1 protects against cerebral ischemia–reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway

Xin Xu, Weiwei Gao, Lei Li et al.

Abstract Background Cerebral ischemia–reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated. Methods We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen–glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization. Results The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2–3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood–brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5’ adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments. Conclusions Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.

Neurology. Diseases of the nervous system
DOAJ Open Access 2014
Prevalência de sintomas depressivos e ansiosos em pacientes com dor crônica

Ricardo Cardoso Pinheiro, Ricardo Riyoiti Uchida, Lígia Andrade da Silva Telles Mathias et al.

Objetivos O presente estudo objetivou avaliar a prevalência de sintomas ansiosos e depressivos e relacioná-los com os diferentes tipos e magnitudes de dor crônica; também objetivou caracterizar a população de casos novos agendados para atendimento no ambulatório de dor crônica, no serviço onde o estudo foi realizado. Métodos Estudo de corte transversal, realizado em um ambulatório docente-assistencial para tratamento de dor crônica, realizado entre maio de 2012 e abril de 2013, com 125 pacientes. Instrumentos utilizados Questionário sociodemográfico, Escala Hospitalar de Ansiedade e Depressão (HAD) e Escala Visual Numérica (EVN) para aferir a intensidade de dor. Resultados Dor intensa foi referida por 64% (n = 80) dos pacientes. Ansiedade atingiu 65% (N = 82) dos pacientes e a depressão, 48% (N = 60). Houve correlação significante entre os mais altos escores de ansiedade (p < 0,001) e depressão (p < 0,001) com a intensidade de dor. A correlação entre intensidade de dor e sintomas ansiosos e depressivos foi positiva para dor crônica neuropática e mista. Os fatores sociodemográficos associados à intensidade de dor crônica foram: renda e religião para depressão, e tempo de dor para ansiedade. Conclusão O estudo mostrou elevada prevalência de sintomas depressivos e ansiosos em pacientes com dor crônica, assim como relação significante desses sintomas psiquiátricos com alguns tipos e intensidade de dor.

DOAJ Open Access 2014
Psychometric Properties of the Intolerance of Uncertainty Scale (IUS) in a Lithuanian-speaking population

Augustinas Rotomskis

<p class="p1">Research suggests that intolerance of uncertainty may be important in understanding worry and may play a key role in the etiology and maintenance of worry. Intolerance of uncertainty is measured using the Intolerance of Uncertainty Scale (IUS), which has been shown to be reliable and valid in many studies. The aim of the present study was to develop a Lithuanian version of this instrument. 228 university students completed the scale. The Lithuanian version of the IUS was found to have good psychometric properties. The IUS showed high internal consistency and good test-retest reliability over a five-week period, and good convergent and divergent validity when assessed with measures of trait anxiety, situational anxiety, and depression. Factor analysis indicated that the IUS has a two-factor structure that represents the beliefs that “uncertainty about the future is unfair” and that “uncertainty has negative behavioral and self-referent implications”. In conclusion, it was found that the Lithuanian version of the IUS is a sound scale for assessing intolerance of uncertainty. </p>

Neurosciences. Biological psychiatry. Neuropsychiatry, Psychology
DOAJ Open Access 2014
Supported employment among veterans with serious mental illness: the role of cognition and social cognition on work outcome

L. Felice Reddy, Robert S. Kern

Unemployment is a primary functional deficit for the majority of adults with schizophrenia. Research indicates that over two-thirds of adults living in the community with schizophrenia are unemployed. Despite effective programs to assist with job identification and placement, the ability to attain and maintain employment remains a pressing concern. Neurocognitive functioning is widely acknowledged to be a determinant of work outcome; however, effect sizes tend to be in the small to medium range. The present study sought to further understand the determinants of work outcome among a sample of 104 veterans with schizophrenia enrolled in a supported employment program. A small percentage of veterans in the study got competitive jobs; 53% who secured jobs maintained employment for longer than 6 months. Cognition, social cognition, and symptoms were unrelated to job attainment. However, speed of processing and social cognition were significant predictors of work outcomes such as wages and tenure. These findings suggest that cognitive abilities including processing speed and the ability to accurately interpret and respond to social cues are significant determinants of whether individuals with schizophrenia remain employed. The results are discussed in light of current available treatment options and domains to target in synergy with work rehabilitation efforts.

Neurology. Diseases of the nervous system
DOAJ Open Access 2012
Cyanide preconditioning protects brain endothelial and NT2 neuron-like cells against glucotoxicity: Role of mitochondrial reactive oxygen species and HIF-1α

Sónia C. Correia, Renato X. Santos, Sandra M. Cardoso et al.

The current study was undertaken to address the role of mitochondrial reactive oxygen species (ROS), and hypoxia inducible factor-1 alpha (HIF-1α) signaling pathway in the protection against high glucose levels in brain endothelial and NT2 neuron-like cells. Rat brain endothelial cells (RBE4) treated with non-toxic concentrations of cyanide (≤1 μM; 1 h) exhibited an increase in ROS levels, particularly hydrogen peroxide (H2O2). Cyanide also induced a modest mitochondrial depolarization, an increase in oxygen consumption and a structural (smaller mitochondria) and spatial (perinuclear region) reorganization of mitochondrial network. The stabilization and nuclear activation of HIF-1α in the presence of cyanide were also observed, which resulted in an increase in vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and erythropoietin (EPO) protein levels reflecting an adaptive response. Importantly, preconditioning induced by cyanide protected brain endothelial cells against high glucose-mediated damage by the prevention of apoptotic cell death. In mitochondrial DNA-depleted NT2 (NT2 ρ0) cells, cyanide (0.1 μM) was unable to stimulate ROS production and, consequently, protect against glucotoxicity. Conversely, in NT2 cells, the parental cells with functional mitochondria, cyanide significantly increased ROS levels protecting against high glucose-induced neuronal cell loss and activation of caspase-3. The free radical scavenger N-acetyl-L-cysteine and the specific HIF-1α inhibitor 2-methoxyestradiol completely abolished the protective effects of cyanide preconditioning. Altogether our results demonstrate that mitochondrial preconditioning induced by cyanide triggers a protective response mediated by mitochondrial ROS and HIF-1α activation and signaling, which render brain endothelial and neuronal cells resistant against glucotoxicity.

Neurosciences. Biological psychiatry. Neuropsychiatry

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