Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging.Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure.Results: Higher PACAP levels were associated with greater EC NDI (ß = 0.0099, q = 0.032) and lower EC ODI (ß = -0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures.Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.

PACAP was associated with altered entorhinal cortex neurite density in PTSD.PACAP was not associated with altered neurite density in amygdala or hippocampus.PACAP may impact arousal-associated memory circuits.

Exercise induction at expression immediate early gene (c-Fos, ARC, EGR-1) in the hippocampus: a systematic review / Indução de exercício físico na expressão do gene precoce imediato (c-Fos, ARC, EGR-1) no hipocampo: uma revisão sistemática

ABSTRACT. The immediate early gene exhibits activation markers in the nervous system consisting of ARC, EGR-1, and c-Fos and is related to synaptic plasticity, especially in the hippocampus. Immediate early gene expression is affected by physical exercise, which induces direct ARC, EGR-1, and c-Fos expression. Objective: To assess the impact of exercise, we conducted a literature study to determine the expression levels of immediate early genes (ARC, c-Fos, and EGR-1). Methods: The databases accessed for online literature included PubMed-Medline, Scopus, and ScienceDirect. The original English articles were selected using the following keywords in the title: (Exercise OR physical activity) AND (c-Fos) AND (Hippocampus), (Exercise OR physical activity) AND (ARC) AND (Hippocampus), (Exercise OR physical activity) AND (EGR-1 OR zif268) AND (Hippocampus). Results: Physical exercise can affect the expression of EGR-1, c-Fos, and ARC in the hippocampus, an important part of the brain involved in learning and memory. High-intensity physical exercise can increase c-Fos expression, indicating neural activation. Furthermore, the expression of the ARC gene also increases due to physical exercise. ARC is a gene that plays a role in synaptic plasticity and regulation of learning and memory, changes in synaptic structure and increased synaptic connections, while EGR-1 also plays a role in synaptic plasticity, a genetic change that affects learning and memory. Overall, exercise or regular physical exercise can increase the expression of ARC, c-Fos, and EGR-1 in the hippocampus. This reflects the changes in neuroplasticity and synaptic plasticity that occur in response to physical activity. These changes can improve cognitive function, learning, and memory. Conclusion: c-Fos, EGR-1, and ARC expression increases in hippocampal neurons after exercise, enhancing synaptic plasticity and neurogenesis associated with learning and memory.

RESUMO. O gene precoce imediato (GPI) exibe marcadores de ativação no sistema nervoso constituídos por ARC, EGR-1 e c-Fos e está relacionado à plasticidade sináptica, especialmente no hipocampo. A expressão do GPI é afetada pelo exercício físico, que induz a expressão direta de ARC, EGR-1 e c-Fos. Objetivo: Para avaliar o impacto do exercício físico, realizamos um estudo de literatura para determinar os níveis de expressão dos GPIs (ARC, c-Fos e EGR-1). Métodos: A base de dados utiliza literatura on-line, PubMed-Medline, Scopus e ScienceDirect. O artigo original em inglês usa as seguintes palavras-chave em seu título: (Exercise) AND (c-Fos) AND (Hippocampus), (Exercise) AND (ARC) AND (Hippocampus), (Exercise) AND (EGR-1) AND (Hippocampus). Resultados: O exercício físico pode afetar a expressão de EGR-1, c-fos e ARC no hipocampo, uma parte importante do cérebro envolvida na aprendizagem e na memória. O exercício físico aumenta a expressão do gene c-Fos; sua alta intensidade pode aumentar a expressão de c-Fos, indicando ativação neural. Além disso, a expressão do gene ARC aumentou devido ao exercício físico, onde ARC é um gene que desempenha um papel na plasticidade sináptica e na regulação da aprendizagem e da memória, nas mudanças na estrutura sináptica e no aumento das conexões sinápticas, enquanto o EGR-1 também desempenha um papel na plasticidade sináptica, uma mudança genética que afeta o aprendizado e a memória. De maneira geral, o exercício físico regular pode aumentar a expressão de ARC, c-fos e EGR-1 no hipocampo. Isso reflete as mudanças na neuroplasticidade e na plasticidade sináptica que ocorrem em resposta à atividade física. Essas mudanças podem melhorar a função cognitiva, o aprendizado e a memória. Conclusão: A expressão de c-Fos, EGR-1 e ARC aumenta após o exercício físico nos neurônios do hipocampo, para aumentar a plasticidade sináptica, a neurogênese associada ao aprendizado e à memória.

Epilepsia do lobo temporal com esclerose hipocampal mesial / Temporal lobe epilepsy with mesial hippocampal sclerosis / Epilepsia del lóbulo temporal con esclerosis del hipocampo mesial

Objetivo:Compreender o cenário atual da ELT-HS, caracterizado por sua fisiopatologia, manifestações clínicas, métodos diagnósticos e tratamentos. Método:Trata-se de uma revisão integrativa da literatura, com caráter descritivo, de artigos indexados no Sistema de Análise e Recuperação da Literatura Médica Online MEDLINE/Pubmed, Literatura Latino-Americana e do Caribe em Ciências da Saúde LILACS, e nas bases de dados Científicas Electronic Library Online (SciELO), pesquisados na período compreendido entre outubro de 2022 e março de 2023. Foram incluídos artigos em português e inglês que contemplassem os objetivos da revisão, publicados nos últimos dez anos (2011-2021).Resultados: Inicialmente foram encontrados 144 artigos nas bases de dados, que após a leitura, foramselecionados na pesquisa 40 artigos que correspondiam ao objetivo proposto. Os artigos analisados correspondem aos anos de 2011 a 2021. Conclusão:O tratamento cirúrgico da ELT-HS tem se mostrado eficaz para resolução completa das crises na maioria dos pacientes. O conhecimento sobre sua fisiopatologia, manifestações clínicas, diagnóstico e tratamentos são de fundamental importância para os médicos que atendem pacientes com epilepsia.

Objective: To understand the current scenario of TLE-HS, characterized by its pathophysiology, clinical manifestations, diagnostic methods and treatments. Method:This is an integrative literature review with descriptive character, of articles indexed in the Medical Literature Analysis And Retrieval System Online MEDLINE/Pubmed, Latin American and Caribbean Literature in Health Sciences LILACS, and Scientic databases Electronic Library Online (SciELO), researched in the period between october 2022 and march 2023. Articles in Portuguese and English that contemplated the objectives of the review, published in the last ten years (2011-2021), were included. Results:Initially, 144 articles were found in the databases, which after reading, 40 articles were selected in the research that corresponded to the proposed objective. The articles analyzed are equivalent to the years 2011 to 2021. Conclusion:The surgical treatment of TLE-HS has been shown to be effective for the complete resolution of crises in most patients. Knowledge about its pathophysiology, clinical manifestations, diagnosis and treatments are of fundamental importance for physicians who treat patients with epilepsy

Objetivo: Comprender el escenario actual de la TLE-HS, caracterizado por su fisiopatología, manifestaciones clínicas, métodos diagnósticos y tratamientos. Método: Se trata de una revisión bibliográfica integradora con carácter descriptivo, de artículos indexados en el Sistema de Análisis y Recuperación de Literatura Médica en Línea MEDLINE/Pubmed, Literatura Latinoamericana y del Caribe en Ciencias de la Salud LILACS, y bases de datos Scientic Electronic Library Online (SciELO), investigados en el período comprendido entre octubre de 2022 y marzo de 2023. Se incluyeron artículos en portugués e inglés que contemplaran los objetivos de la revisión, publicados en los últimos diez años (2011-2021). Resultados:Inicialmente se encontraron 144 artículos en las bases de datos, de los cuales luego de la lectura se seleccionaron 40 artículos en la investigación que correspondía al objetivo propuesto. Los artículos analizadoscorresponden a los años 2011 a 2021. Conclusión:El tratamiento quirúrgico del ELT-HS se ha mostrado eficaz para la resolución completa de las crisis en la mayoría de los pacientes. El conocimiento sobre su fisiopatología, manifestaciones clínicas, diagnóstico y tratamientos es de fundamental importancia para los médicos que tratan pacientes con epilepsia

Correlación entre escalas visuales de atrofia entorrinal y temporomesial con volumetría hipocampal / Correlation between visual scales of entorhinal and temporomesial atrophy with hippocampal volumetry

Resumen Objetivo: En pacientes con enfermedad de Alzheimer (EA) se han descrito cambios neuropatológicos tempranos en la corteza entorrinal, que anteceden el compromiso temporomesial. La evaluación de la atrofia hipocampal mediante escalas visuales y volumetría son herramientas útiles en la valoración de pacientes con deterioro cognitivo. Nuestro objetivo es establecer la correlación entre la evaluación visual de la atrofia de la corteza entorrinal (ACE), la atrofia temporomesial (ATM) y el volumen hipocampal. Material y métodos: Estudio retrospectivo de corte transversal. Se incluyeron pacientes con queja cognitiva y resonancia magnética (RM) cerebral. Se utilizaron escalas visuales de ACE y ATM. Se midió el volumen hipocampal mediante el software volBrain 1.0. Resultados: Se incluyeron 48 pacientes, 31 eran mujeres (64,6%). Mediana de edad: 76,5 (RIQ: 69-83). La correlación entre las escalas visuales ACE y la ATM del lado derecho fue de 0,67 p < 0,0001) y del lado izquierdo de 0,69 (p < 0,0001). Encontramos correlación negativa moderada entre la ACE y el volumen hipocampal, del lado derecho fue de –0,59 (p < 0,0001) y del lado izquierdo de –0,42 (p = 0,003). Conclusión: La escala de ACE muestra moderada correlación con la escala de ATM y con el volumen hipocampal. Su uso podría aportar información valiosa para valoración de trastornos cognitivos.

Abstract Objective: In patients with Alzheimer’s disease (AD), early neuropathological changes in the entorhinal cortex have been described, which precede temporomesial involvement. The evaluation of hippocampal atrophy using visual scales and volumetry are useful tools in the assessment of patients with cognitive impairment. Our objective is to establish the correlation between the visual evaluations of entorhinal cortex atrophy (ECA), temporomesial atrophy (TMA), and hippocampal volume. Material and methods: Retrospective cross-sectional study. Patients with cognitive complaint and brain magnetic resonance imaging (MRI) were included. ACE and TMA visual scales were used. Hippocampal volume was measured using the volBrain 1.0 software. Results: Forty-eight patients were included, 31 were women (64.6%). Median age was 76.5 (IQR: 69-83). The correlation between ECA and TMA on the right side was 0.67 (p < 0.0001) and on the left side was 0.69 (p < 0.0001). We found a negative moderate correlation between ECA and hippocampal volume, on the right side it was –0.59 (p < 0.0001) and on the left side it was –0.42 (p = 0.003). Conclusion: The ECA scale shows high correlation with the TMA scale and moderate correlation with hippocampal volume. Its use could provide valuable information for the assessment of cognitive disorders.

The stress-buffering role of friendships in young people with childhood threat experiences: a preliminary report.

Background: High-quality friendships have a positive impact on the mental health of young people with childhood adversity (CA). Social stress buffering, the phenomenon of a social partner attenuating acute stress responses, is a potential yet unexplored mechanism that may underlie this relationship.Objective: This study examined whether perceived friendship quality was related to better mental health and lower neural stress response in young people with CA.Method: A total of N = 102 young people (aged 16-26) with low to moderate CA were included in the study. We first investigated associations between friendship quality, mental health, and CA. In a representative subset (n = 62), we assessed neural stress responses using the Montreal Imaging Stress Task. In our sample, CA was best described along two dimensions resembling threat or deprivation like experiences. Hence, we investigated both cumulative and dimensional effects of CA.Results: We found no support for social thinning after CA, meaning that the severity of CA (cumulative or dimensional) did not differentially impact friendship quality. High-quality friendships, on the other hand, were strongly associated with better mental health. Furthermore, acute stress increased state anxiety and enhanced neural activity in five frontolimbic brain regions, including the left hippocampus. We found weak support that threat experiences interacted with friendship quality to predict left hippocampal reactivity to stress. However, this effect did not survive multiple comparison correction.Conclusion: The absence of social thinning in our sample may suggest that the risk of developing impoverished social networks is low for rather well-functioning young people with low to moderate CA. Regardless, our findings align with prior research, consistently showing a strong association between high-quality friendships and better mental health in young people with CA. Future research is needed to examine whether friendships aid neural stress responses in young people with childhood threat experiences.

Young people with childhood adversity underwent acute stress induction, eliciting frontolimbic reactivity.High-quality friendships were strongly associated with better mental health.Weak support for friendship stress buffering did not survive multiple comparison correction.

Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Epileptogénesis y corteza piriforme: entendiendo a la epilepsia del lóbulo temporal más allá del hipocampo / Epileptogenesis and the piriform cortex: understanding temporal lobe epilepsy beyond the hippocampus

Introducción: Con la experiencia de los registros electroencefalográficos invasivos y el fracaso quirúrgico después de la cirugía, se ha hecho evidente que la epilepsia del lóbulo temporal es mucho más compleja de lo que se creía, y en la actualidad es considerada una enfermedad de redes anatomofuncionales y no de lesiones estructurales. Contenido: La información neurofisiológica e imagenológica actual permite concluir que en esta epilepsia están involucradas varias redes neuronales temporales y extratemporales que contribuyen a la extensión de la zona epileptógena. Una forma de entender el concepto de red epiléptica en la epilepsia del lóbulo temporal es a partir del conocimiento de la corteza piriforme. Varios estudios clínicos han mostrado que en pacientes con epilepsia del lóbulo temporal asociada a esclerosis hipocampal existe una disfunción interictal del procesamiento olfatorio que es más significativa, en comparación con pacientes con epilepsia focal extrahipocampal y controles sanos. Esta alteración es, probablemente, la consecuencia de una red neuronal disfuncional que se extiende más allá del hipocampo y que afecta a otras estructuras cercanas, incluida la corteza piriforme. Conclusión: En este artículo llevamos a cabo una revisión narrativa de la literatura con el objetivo de establecer un vínculo entre la corteza piriforme y la epileptogénesis del lóbulo temporal, y demostramos que esta enfermedad es la consecuencia de una disfunción de redes neuronales que no depende exclusivamente de una anormalidad estructural en el hipocampo o en estructuras cercanas.

Introduction: With the experience of invasive EEG recordings and surgical failure after surgery, it has become clear that temporal lobe epilepsy is much more complex than previously thought, and currently, is conceptualized as a disease of anatomical networks instead of structural lesions. Content: The current neurophysiological and imaging information allows us to conclude that several temporal and extratemporal anatomical networks are involved in this type of epilepsy. One way of understanding the concept of the epileptic network in temporal lobe epilepsy is from the knowledge of the piriform cortex. Several clinical studies have shown that in patients with temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that is more significant compared to patients with focal extra-hippocampal epilepsy and healthy controls. This alteration is probably the consequence of a dysfunctional neural network that extends beyond the hippocampus and affects other nearby structures, including the piriform cortex. Conclusion: In this article, we carry out a narrative review of the literature with the aim of establishing a link between the piriform cortex and temporal lobe epileptogenesis, demonstrating that this disease is the consequence of a dysfunctional network that does not depend exclusively of a hippocampal structural abnormality.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

Rhinal and hippocampal event-related potentials as epileptogenic zone markers in the pre-surgical evaluation of temporal epilepsies: a systematic review / Potenciais evocados rinais e hipocampais como marcadores da zona epileptogênica na avaliação pré-cirúrgica das epilepsias temporais: uma revisão sistemática

Abstract Background Cognitive event-related potentials (ERPs) allow for lateralization of the epileptogenic zone (EZ) to estimate the reserve of memory in the contralateral non-epileptogenic hemisphere, and to investigate the prognosis of temporal lobe seizure control in unilateral temporal lobe epilepsy (TLE). Objective To define the accuracy of cognitive evoked anterior mesial temporal lobe (AMTL-N400) and P600 potentials in detecting the epileptogenic zone in temporal lobe epilepsy (TLE), and second, to evaluate the possibility of using them as markers of cognitive outcome. Methods The systematic review using Medline/PubMed, Embase, and Lilacs database was conducted in September 2021. Only articles published in English from 1985 to June 2021 were included. We searched for studies with: (1) depth intracranial electroencephalography (iEEG) recordings analysis of rhinal and hippocampal activity (2) correlations between ERP results obtained in the mesial temporal regions (AMTL-N400 and P600) and the epileptogenic zone. Results Six out of the seven studies included in this review defined the laterality of the epileptogenic zone (EZ) during presurgical investigation using ERPs. One study showed that the contralateral AMTL-N400 predicts seizure control. Another study found correlation between the amplitudes of the right AMTL-N400 and postoperative memory performance. Conclusions There is evidence that the reduced amplitude of the AMTL-N400 has high accuracy in identifying the epileptogenic zone, as it does in estimating the extent of seizure control and memory impairment in postoperative patients.

Resumo Antecedentes Potenciais relacionados a eventos (PREs) cognitivos permitem a lateralização da zona epileptogênica (ZE), estimar a reserva de memória no hemisfério contralateral não-epileptogênico, e estimar o prognóstico pós-operatório em pacientes com epilepsia do lobo temporal (ELT) unilateral quanto ao controle de crises. Objetivo Definir a acurácia dos potenciais evocados cognitivos do lobo temporal mesial anterior (LTMA-N400) e P600 na detecção da zona epileptogênica na epilepsia do lobo temporal (ELT), além de avaliar a possibilidade de usá-los como marcadores de desfecho cognitivo. Métodos A revisão sistemática foi realizada em setembro de 2021 usando as bases de dados Medline/PubMed, Embase e Lilacs. Apenas artigos publicados em inglês no período entre 1985 e junho de 2021 foram incluídos. Buscamos estudos com: (1) análises dos registros de electroencefalografia intracraniana (EEGi) da atividade rinal e hipocampal (2) correlações entre os resultados de PREs obtidos nas regiões temporais mesiais (AMTL-N400 e P600) e a zona epileptogênica. Resultados Seis dos sete estudos incluídos nesta revisão definiram a lateralidade da zona epileptogênica (ZE) durante a investigação pré-cirúrgica usando PREs. Um estudo mostrou que o AMTL-N400 contralateral prediz o controle das crises. Outro estudo encontrou correlação entre as amplitudes do AMTL-N400 direito e o desempenho da memória pós-operatória. Conclusões Há evidências de que a amplitude reduzida do AMTL-N400 tem alta precisão na identificação da zona epileptogênica, assim como na estimativa do prognóstico quanto ao controle de crises a longo prazo e prejuízo da memória em pacientes submetidos à cirurgia ressectiva.

Concentraciones de oxígeno intermitentes tienen impacto en el desarrollo postnatal temprano de ratas Sprague-Dawley: efectos en CA1 del hipocampo / Intermittent oxygen concentrations have an impact on the early postnatal development of Sprague-Dawley rats: effects on hippocampal CA1

El periodo postnatal temprano se caracteriza por rápido crecimiento cerebral, posiblemente relacionado con variaciones del oxígeno tisular. Esto ha motivado el estudio de protocolos que suministran diferentes concentraciones de oxígeno intermitentes, para observar sus efectos morfológicos y cerebrales. Se utilizaron 52 crías de ratas Sprague Dawley, distribuidas en igual número a cuatro grupos experimentales, Control (C, 21 %O2), Hipoxia Intermitente (HI, 11 %O2), Hiperoxia Intermitente (HOI, 30 %O2) e Hipoxia Hiperoxia Intermitente (HHI, 11 % -30 %O2). Los protocolos consideraron 5 ciclos de 5 minutos de dosificación, durante 50 minutos diarios. Se realizó en una cámara semihermética entre los días 5 al 11 postnatales. Las evaluaciones de crecimiento corporal y cuantificación neuronal, se realizaron en las crías macho, en el día 28 postnatal. El peso corporal en el grupo hipoxia intermitente mostró diferencias significativas respecto al grupo hiperoxia intermitente (HI vs HOI, p<0,01) y al grupo hipoxia-hiperoxia Intermitente (HI vs HHI, p< 0,001). La talla corporal disminuyó en el grupo hipoxia-hiperoxia intermitente con diferencias significativas respecto del grupo control (C vs HHI, p<0,05) y respecto del grupo hipoxia intermitente (HHI vs HI, p< 0,01). El conteo neuronal en el área CA1 del hipocampo aumentó en el grupo hipoxia intermitente con diferencias significativas respecto a los grupos control (C vs HI; p<0,05), al grupo hiperoxia intermitente (HI vs HOI; p<0,001) y al grupo hipoxia-hiperoxia intermitente (HI vs HHI; p<0,001). Finalmente, el grupo hipoxia- hiperoxia Intermitente disminuyó significativamente en la cantidad de neuronas en comparación al grupo hiperoxia intermitente (HHI vs HOI; p<0,001). La hipoxia intermitente mostró resultados beneficiosos en el crecimiento corporal y cantidad de neuronas en el área CA1 del hipocampo, en contraste, la hipoxia hiperoxia intermitente experimentó resultados adversos con disminución de estas variables, en el periodo postnatal temprano de la rata.

SUMMARY: The early postnatal period is characterized by rapid brain growth, possibly related to variations in tissue oxygen. This has motivated the study of protocols that supply different intermittent oxygen concentrations, to observe their morphological and cerebral effects. Fifty-two pups Sprague-Dawley rats were distributed in equal numbers into four experimental groups, Control (C, 21 %O), Intermittent Hypoxia (HI, 11 %O), Intermittent Hyperoxia (HOI, 30 %O2) and Intermittent Hypoxia Hyperoxia (HHI, 11 % - 30 %O2). The protocols considered 5 cycles of 5 min of dosing, for 50 min diary. It was performed in a semi- hermetic chamber between 5 to 11postnatal days. The evaluations of body growth and neuronal quantification were analyzed in male pups, on postnatal day 28. Body weight in the intermittent hypoxia group showed significant differences compared to the intermittent hyperoxia group (HI vs HOI, p<0.01) and the intermittent hypoxia- hyperoxia group (HI vs HHI, p<0.001). Body size decreased in the Intermittent hypoxia-hyperoxia group with significant differences compared to the control group (C vs HHI, p<0.05) and with respect to the intermittent hypoxia group (HHI vs HI, p<0.01). The neuronal count in the area CA1 of the hippocampus increased in the intermittent hypoxia group with significant differences compared to the control groups (C vs HI; p<0.05), to the intermittent hyperoxia group (HI vs HOI; p< 0.001) and the intermittent hypoxia-hyperoxia group (HI vs HHI; p<0.001). Finally, the intermittent hypoxia- hyperoxia group decreased significantly in the number of neurons compared with the intermittent hyperoxia group (HHI vs HOI; p<0.001). Intermittent hypoxia showed beneficial results in body growth and the number of neurons in the CA1 area of the hippocampus, in contrast, intermittent hypoxia-hyperoxia experienced adverse results with a decrease in these variables, in the early postnatal period of the rat.

Amnesia global transitoria: una entidad infrecuente pero presente en Pediatría / Transient global amnesia: an infrequent entity but present in Pediatrics

Introducción: La amnesia global transitoria es una entidad caracterizada por la aparición súbita de amnesia anterógrada con amnesia retrógrada variable, conservando intacta la memoria inmediata. No asocia otros déficits neurológicos. La recuperación es progresiva en pocas horas, habitualmente menos de 12, aunque suele persistir amnesia del episodio y presentar posteriormente cefalea leve. Caso clínico. Niño de 10 años, sin antecedentes de interés, que consulta en Urgencias por aparición brusca de amnesia retrógrada de las últimas 48 horas, así como incapacidad para la fijación de nueva información. Se mostraba ansioso y desorientado, y repetía la misma pregunta varias veces. La exploración neurológica por lo demás era estrictamente normal y negaba cefalea u otra sintomatología asociada. No antecedente de traumatismo craneoencefálico. Se realiza analítica sanguínea y gasometría venosa, sin alteraciones significativas; tóxicos en orina, negativos; TAC cerebral que descarta patología intracraneal aguda y punción lumbar, que es normal. Ingresa en planta de hospitalización con evolución favorable, con cese espontáneo de la clínica a las 8 horas, permaneciendo amnesia del episodio, con resto de la memoria conservada. Comentarios. La fisiopatología de la amnesia global transitoria no está del todo aclarada, aunque hay trabajos que sugieren un origen vascular de la misma, produciéndose durante estos episodios una hipoperfusión del lóbulo temporal medial. Es una entidad típica de adultos de mediana edad y ancianos siendo excepcional en pediatría. Sin embargo, debemos considerar este diagnóstico ante niños con clínica típica, normalidad de la neuroimagen y resolución espontánea de los síntomas.(AU)

Introduction: Transient global amnesia is an entity characterized by the sudden onset of anterograde amnesia with variable retrograde amnesia, preserving immediate memory intact. It is not associated with other neurological deficits. Recovery is progressive in a few hours, usually less than 12 hours, although amnesia of the episode usually persists and later presents mild headache. Case report. A 10-year-old boy, with no previous history of interest, consulted the emergency department for sudden onset of retrograde amnesia of the last 48 hours, as well as inability to fix new information. He was anxious and disoriented and repeated the same question several times. The neurological examination was otherwise strictly normal, and he denied headache or other associated symptoms. There was no history of cranioencephalic trauma. Blood analysis and venous blood gas analysis were performed, with no significant alterations; urine toxins were negative; brain CAT scan ruled out acute intracranial pathology and lumbar puncture was normal. She was admitted to the hospital ward with favorable evolution, with spontaneous cessation of the clinical symptoms after 8 hours, remaining amnesia of the episode, with the rest of the memory preserved. Comments. The pathophysiology of transient global amnesia has not been fully clarified, although some studies suggest a vascular origin, with hypoperfusion of the medial temporal lobe occurring during these episodes. It is a typical entity of middle-aged and elderly adults, being exceptional in pediatrics. However, we should consider this diagnosis in children with typical clinical symptoms, normal neuroimaging and spontaneous resolution of symptoms.(AU)

MTL-P300 as a marker of the epileptogenic zone and hippocampal functionality in the presurgical evaluation of temporal lobe epilepsy: a systematic review / MTL-P300 como um marcador da zona epileptogênica e da funcionalidade hipocampal na avaliação pré-operatória da epilepsia do lobo temporal: revisão sistemática

Abstract Background In the past twenty years, there has been an increasing interest among neuroscientists and physicians in mapping the cortical areas involved in the epileptogenic zone (EZ) through event-related potentials (ERPs) that enable the evaluation of the functional preservation of these areas. The present review is an update on publications on this topic. Objective To investigate the accuracy of the cognitive evoked of the medial temporal lobe P300 (MTL-P300) potential in detecting the EZ in temporal lobe epilepsy (TLE). Methods The systematic review of articles on the PubMed, Embase and Lilacs databases was conducted between February and December 2020. Articles published in English from 1985 to December 2020 were included. Additional studies were identified by searching the references of the selected studies and review articles. The studies were included for the following reasons: in-depth intracranial electroencephalography (iEEG) analysis of hippocampal activity; investigations of patients with TLE; and correlations between regarding the ERP results obtained in the temporal regions (MTL-P300) and the EZ. Results In the three studies analyzed, the authors were able to define the laterality of the EZ during the preoperative investigation through the MTL-P300 results. The sensitivity of this method was of ~ 70% to 80%, and the specificity between 70% and 94.7%. One of the limitations of the present review was the low number of studies. Conclusion There is evidence that the reduced amplitude of the MTL-P300 has high specificity in identifying the EZ, and this is a good marker for diagnosis in unilateral TLE. The low sensitivity and negative likelihood ratios negative that a normal MTL-P300 response does not exclude the epileptogenicity of the hippocampus.

Resumo Antecedentes Nos últimos 20 anos, tem havido um crescente interesse de neurocientistas e médicos em mapear áreas corticais envolvidas na zona epileptogênica (ZE) por meio de potenciais relacionados a eventos (PREs), que permitem avaliar a preservação funcional dessas áreas. Esta revisão é uma atualização das publicações sobre esse tema. Objetivo Investigar a acurácia do potencial evocado cognitivo do lobo temporal medial P300 (medial temporal lobe P300, MTL-P300, em inglês) na detecção da ZE em casos de epilepsias do lobo temporal (ELT). Métodos A revisão sistemática de artigos nas bases de dados PubMed, Embase e Lilacs foi realizada entre fevereiro e dezembro de 2020. Foram incluídos artigos publicados em inglês de 1985 a dezembro de 2020. Estudos adicionais foram identificados por meio de busca nas referências dos estudos selecionados e artigos de revisão. Os estudos foram incluídos pelas seguintes razões: análise detalhada por meio de eletroencefalografia intracraniana (iEEG) da atividade hipocampal; investigações de pacientes com ELT; e correlações entre os resultados de ERP obtidos nas regiões temporais (MTL-P300) e na ZE. Resultados Nos três estudos analisados, os autores foram capazes de definir a lateralidade da ZE durante a investigação pré-operatória por meio dos resultados do MTL-P300. A sensibilidade deste método foi de 70% a 80%, e a especificidade, entre 70% e 94.7%. Uma das limitações desta revisão foi o baixo número de estudos. Conclusão Há evidências de que a amplitude reduzida do MTL-P300 tem alta especificidade na identificação da ZE, e este é um bom marcador para o diagnóstico na ELT unilateral. A baixa sensibilidade e a razão de verossimilhança negativa indicam que a resposta MTL-P300 normal não exclui a epileptogenicidade do hipocampo.

Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer / Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease

Introducción: En el mundo, alrededor de 50 millones de personas padecen demencia; la forma más común es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo diseñar estudios que permitan ampliar el conocimiento sobre su aparición y desarrollo, para proponer diagnósticos tempranos y/o posibles tratamientos. Una de las estrategias metodológicas que se han desarrollado son los modelos transgénicos murinos para el estudio de los factores involucrados en su etiología, y entre ellos, el estrés oxidativo y la respuesta inmune.DesarrolloSe realizó una búsqueda de artículos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revisión abordamos dos factores que han sido estudiados de forma independiente: el estrés oxidativo y la respuesta inmune en modelos transgénicos para la EA, y se discute la relación que existe entre ellos y que impacta en la pérdida de la plasticidad sináptica y estructural, produciendo como efecto final el deterioro cognitivo.ConclusiónEsta revisión describe posibles mecanismos en donde participan el estrés oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relación entre estos elementos que conducen hacia el deterioro cognitivo. (AU)

Introduction: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response.DevelopmentWe searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment.ConclusionThis review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment. (AU)

Signos radiológicos en la neuroimagen de pacientes pediátricos con trastorno por estrés postraumático / Radiological signs in neuroimaging of pediatric patients with posttraumatic stress disorder

RESUMEN Introducción: El trastorno por estrés postraumático afectan la salud mental de los pacientes pediátricos, se considera muy común en estos pacientes. Estudios científicos apoyados en la resonancia magnética han fundamentado una estrecha relación entre el estrés postraumático y cambios estructurales en el cerebro. Se realizó una revisión bibliográfica en el periodo de abril a mayo de 2021, en los recursos disponibles en MEDLINE, SciELO, Pubmed y Elsevier. Del total de consultas se citaron 25 referencias. Objetivo: Describir los signos radiológicos en la neuroimagen de pacientes pediátricos con estrés postraumático. Desarrollo: Los estudios de neuroimagen en niños y adolescentes con trastorno por estrés postraumático se han centrado en estructuras anormales y la funcionalidad de algunas regiones individuales del cerebro; estas implican las regiones cerebrales asociadas con la fisiopatología, ellas son: la corteza prefrontal medial y dorsolateral; la corteza orbitofrontal; ínsula; núcleo lentiforme; amígdala; hipocampo y el parahipocampo; la corteza cingulada anterior y posterior; el precúneo; cúneo; el giro fusiforme y lingual y los tractos de materia blanca que conectan estas regiones cerebrales. Conclusiones: Los signos radiológicos en la neuroimagen de pacientes pediátricos con trastorno por estrés postraumático son: reducción de los volúmenes del hipocampo; del volumen cerebral e intracraneal y del volumen de la amígdala, así como una disminución del área total del cuerpo calloso. Además se observa que el volumen hipofisario y los volúmenes de materia gris cerebral fueron menores en los pacientes con estrés postraumático.

ABSTRACT Introduction: Post-traumatic stress disorder affects the mental health of pediatric patients; it is considered very common in these patients. Scientific studies supported by magnetic resonance imaging have established a close relationship between post-traumatic stress and structural changes in the brain. A bibliographic review was carried out in the period from April to May 2021, in the resources available in MEDLINE, SciELO, Pubmed and Elsevier. Of the total of consultations, 25 references were cited. Objective: To describe the radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder. Development: Neuroimaging studies in children and adolescents with post-traumatic stress disorder have focused on abnormal structures and the functionality of some individual brain regions; these involve the brain regions associated with pathophysiology, they are: the medial and dorsolateral prefrontal cortex; the orbitofrontal cortex; insula; lentiform nucleus; amygdala; hippocampus and parahippocampus; the anterior and posterior cingulate cortex; the precuneus; cuneus; the fusiform and lingual gyrus and the white matter tracts that connect these brain regions. Conclusions: The radiological signs in the neuroimaging of pediatric patients with post-traumatic stress disorder are: reduction of the volumes of the hippocampus; brain and intracranial volume and amygdala volume, as well as a decrease in the total area of ​​the corpus callosum. In addition, it is observed that the pituitary volume and the volumes of cerebral gray matter were lower in patients with post-traumatic stress.

Activación de la microglía en el hipocampo asociada con lesión del nervio facial / Facial nerve injury-associated hippocampal microglíal activation

Introducción. Las lesiones del nervio facial afectan la plasticidad a largo plazo en el hipocampo, así como la memoria de reconocimiento de objetos y la memoria espacial, dos procesos dependientes de esta estructura. Si bien se ha descrito una activación de la microglía en la corteza motora primaria asociada con esta lesión, no se conoce si ocurre algo similar en el hipocampo. Objetivo. Caracterizar en ratas el efecto de la lesión unilateral del nervio facial sobre la activación de células de la microglía en el hipocampo contralateral. Materiales y métodos. Se hicieron experimentos de inmunohistoquímica para detectar células de la microglía en el hipocampo de ratas sometidas a lesión irreversible del nervio facial. Los animales se sacrificaron en distintos momentos después de la lesión, para evaluar la evolución de la proliferación (densidad de células) y la activación (área celular) de la microglía en el tejido del hipocampo. Los tejidos cerebrales de los animales de control se compararon con los de animales lesionados sacrificados en los días 1,3, 7, 21 y 35 después de la lesión. Resultados. Las células de la microglía en el hipocampo de animales con lesión del nervio facial mostraron signos de proliferación y activación a los 3, 7 y 21 días después de la lesión. Sin embargo, al cabo de cinco semanas, estas modificaciones se revirtieron, a pesar de que no hubo recuperación funcional de la parálisis facial. Conclusiones. La lesión irreversible del nervio facial produce proliferación y activación temprana y transitoria de las células de la microglía en el hipocampo. Estos cambios podrían estar asociados con las modificaciones electrofisiológicas y las alteraciones comportamentales dependientes del hipocampo descritas recientemente.

Introduction: Facial nerve injury induces changes in hippocampal long-term synaptic plasticity and affects both object recognition memory and spatial memory consolidation (i.e., hippocampus-dependent tasks). Although facial nerve injury-associated microglíal activation has been described regarding the primary motor cortex, it has not been ascertained whether something similar occurs in the hippocampus. Peripheral nerve injury- associated microglíal changes in hippocampal tissue could explain neuronal changes in the contralateral hippocampus. Objective: To characterize the effect of unilateral facial nerve injury on microglíal proliferation and activation in the contralateral hippocampus. Materials and methods: Immunohistochemical experiments detected microglíal cells in the hippocampal tissue of rats that had undergone facial nerve injury. The animals were sacrificed at specific times after injury to evaluate hippocampal microglíal cell proliferation (cell density) and activation (cell area); sham-operated animals were compared to lesioned animals sacrificed 1,3, 7, 21, or 35 days after injury. Results: Facial nerve-injured rats' hippocampal microglíal cells proliferated and adopted an activated phenotype 3- to 21-days post-lesion. Such modifications were transient since the microglíal cells returned to their resting state five weeks after injury, despite the injury's irreversible nature. Conclusions: Facial nerve injury causes the transient proliferation and activation of microglíal cells in the hippocampus. This finding might partly explain the morphological and electrophysiological changes described for CA1 pyramidal neurons and the impairment of spatial memory consolidation which has previously been observed in facial nerve-injured rats.

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address 2 factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease. / Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Longitudinal magnetic resonance evaluation of the schizophrenia model of neonatal lesion in the ventral hippocampus.

OBJECTIVE: To evaluate the progression by means of nuclear magnetic resonance of the lesion in the schizophrenia model of lesion of the ventral hippocampal nucleus (LVNH). METHOD: Magnetic resonance imaging (MRI) were performed in male Wistar rats, from 8 days postnatal to 139 days, in animals with LNHV and without lesion (sham). The MRI were carried out on a Variant 7 T equipment. The data were analyzed with the Amira software, for a voxel-based morphometric analysis. RESULTS: We observed the presence of hypersignals with a significant enhancement in the structures analyzed in the group with LVNH, and greater volume in the lateral ventricles, presenting a larger size of the lesion on day PD96 and significantly reducing on day PD139. CONCLUSIONS: We found a cell rearrangement during the progression of the lesion, which could be the effect of the activation of immune cells.

OBJETIVO: Evaluar mediante resonancia magnética (RM) la progresión de la lesión en el modelo de esquizofrenia de lesión del núcleo del hipocampo ventral (LNHV). MÉTODO: Se realizaron RM en ratas Wistar macho, desde los 8 días posnatales hasta los 139 días, en animales con LNHV y sin lesión (sham). Las RM se realizaron con un equipo Variant de 7 T. Los datos se analizaron con el software Amira para un análisis de morfometría basada en vóxels. RESULTADOS: Observamos hiperseñales con un realce significativo en las estructuras analizadas en el grupo con LNHV, y mayor volumen en los ventrículos laterales, presentando un mayor tamaño de la lesión el día PD96 y significativamente reducido en el día PD139. CONCLUSIONES: Encontramos un reacomodo celular durante la progresión de la lesión, lo cual podría ser efecto de la activación de las células inmunitarias.

Association between childhood trauma and brain anatomy in women with post-traumatic stress disorder, women with borderline personality disorder, and healthy women.

Background: Childhood trauma (CT) is associated with altered brain anatomy. These neuroanatomical changes might be more pronounced in individuals with a psychiatric disorder. Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are more prevalent in individuals with a history of CT. Objective: In this study, we examined limbic and total brain volumes in healthy women with and without a history of CT and in females with PTSD or BPD and a history of CT to see whether neuroanatomical changes are a function of psychopathology or CT. Method: In total, 128 women (N = 70 healthy controls without CT, N = 25 healthy controls with CT, N = 14 individuals with PTSD, and N = 19 individuals with BPD) were recruited. A T1-weighted anatomical MRI was acquired from all participants for Freesurfer-based assessment of total brain, hippocampus, and amygdala volumes. Severity of CT was assessed with a clinical interview and the Childhood Trauma Questionnaire. Group differences in hippocampal and amygdala volumes (adjusted for total brain volume) and total brain volume (adjusted for height) were characterized by analysis of covariance. Results: Volume of the total brain, hippocampus, and amygdala did not differ between the four groups (p > .05). CT severity correlated negatively with total brain volume across groups (r = -0.20; p = .029). Conclusions: CT was associated with reduced brain volume but PTSD or BPD was not. The association between CT and reduced brain volume as a global measure of brain integrity suggests a common origin for vulnerability to psychiatric disorders later in life.

Antecedentes: El trauma infantil (TI) se asocia con alteraciones en la anatomía cerebral. Estos cambios neuroanatómicos pueden ser más pronunciados en individuos con trastornos psiquiátricos. El trastorno de estrés postraumático (TEPT) y el trastorno de personalidad limítrofe (TPL) son más prevalentes en individuos con historia de TI.Objetivo: En este estudio, examinamos los volúmenes límbico y cerebral total en mujeres sanas con y sin historia de TI y mujeres con TEPT o TPL e historia de TI para ver si los cambios neuroanatómicos son una función de la psicopatología o del TI.Método: En total, 128 mujeres (N= 70 controles sanas sin TI, N= 25 controles sanas con TI, N= 14 individuos con TEPT y N= 19 individuos con TPL) fueron reclutadas. Se obtuvo una RNM anatómica ponderada en T1 de todas las participantes para la evaluación basada en Freesurfer de los volúmenes totales del cerebro, hipocampo y amígdala. La severidad del TI fue evaluada con una entrevista clínica y con el Cuestionario de Trauma Infantil. Las diferencias grupales en los volúmenes del hipocampo y amígdala (ajustadas por el volumen cerebral total) y el volumen cerebral total (ajustadas por altura) se caracterizaron mediante análisis de covarianza.Resultados: El volumen total del cerebro, hipocampo y amígdala no difirieron entre los cuatro grupos (p > .05). La severidad del TI se correlacionó negativamente con el volumen cerebral total en todos los grupos (r = −0.20; p =.29).Conclusiones: El TI estuvo asociado a un volumen cerebral reducido, pero el TEPT o TPL no se asociaron. La asociación entre TI y volumen cerebral disminuido como una medida global de la integridad cerebral sugiere un origen común de vulnerabilidad a los trastornos psiquiátricos más adelante en la vida.

Anabolic steroids and their effects of on neuronal density in cortical areas and hippocampus of mice / Esteroides anabolizantes e seus efeitos na densidade neuronal em áreas corticais e no hipocampo de camundongos

Abstract Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.

Resumo As substancias anabólicas tem sido cada vez mais utilizadas por fisiculturistas e atletas com o objetivo de melhorar o desempenho e a estética. No entanto, essa prática tem causado algumas preocupações aos médicos e pesquisadores, devido ao desconhecimento das consequencias que o uso indiscriminado e ilícito dessas substâncias podem causar. Diante disso, este estudo analisou os efeitos de dois esteroides anabolizantes (EA) comercialmente disponíveis, Winstrol Depot® (Stanozolol) e Deposteron® (cipionato de testosterona), na densidade neuronal das regiões corticais límbica, motora e sensitive bem como das áreas CA1, CA2, CA3 do hipocampo. Foram utilizados 60 camundongos Swiss (30 machos e 30 fêmeas), separados em três grupos: controle e dois grupos experimentais, que receberam o EA. De cada cérebro, foram coletadas amostras homotípicas e semi-seriadas em cortes frontais das áreas estabelecidas para o estudo. Os resultados mostraram que as fêmeas tratadas com cipionato de testosterona apresentaram uma redução em todas as regiões analisadas já as fêmeas tratadas com Stanozolol mostraram uma diminuição em algumas áreas do hipocampo. Em relação aos animais machos, o stanozolol levou a uma diminuição na densidade neuronal em uma região do hipocampo. Estes dados nos permitem concluir que doses supra fisiológicas de esteroides utilizadas neste estudo podem causar danos consideráveis ao tecido nervoso com comprometimento ultraestrutural e consequentemente comportamental. Essas alterações podem interferir na perda de rendimento físico e no desempenho de atletas e não atletas e podem causar danos irreparáveis a indivíduos que fazem uso irresponsável destes EA.