Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid-β (Aβ) peptides in the brain. This study demonstrates the direct association of the disposable pipette extraction (DPX) with tandem mass spectrometry (MS/MS) for the analysis of Aβ peptides in cerebrospinal fluid (CSF) samples. Different parameters were optimized in order to improve detectability in the MS/MS including mobile phase percentage of ammonium hydroxide, mobile phase flow rate and acquisition mode. Also, this method used an electrospray ionization (ESI) low-flow probe and direct infusion of an organic solution in the MS/MS. The DPX-MS/MS method showed adequate linearity for determining Aβ peptides in CSF-linearity ranged from 0.1 to 1.5 ng mL 1. The coefficients of determination were higher than 0.99; the precision coefficient of variation (CV) ranged from 0.3 to 12.7%; and the accuracy relative standard deviation (RSD) ranged from -13.6 to 13.2%. Alzheimers Alzheimer s AD (AD amyloidβ amyloid β (Aβ brain DPX (DPX MSMS MS (MS/MS CSF (CSF samples hydroxide mode Also ESI (ESI lowflow low DPXMS/MS DPXMSMS CSFlinearity 01 0 1 0. 15 5 0.99 099 99 CV (CV 03 3 12.7% 127 12 7 RSD (RSD 13.6 136 13 6 -13. 132 2 13.2% DPXMS 0.9 09 9 12.7 13. -13 13.2 12. -1 -

Worldwide, millions of people suffer from neurological and psychiatric conditions, such as schizophrenia, depression, and neurodegenerative diseases. These conditions are often linked to hyperactivity of monoamine oxidase B (MAO-B) in the brain, and inhibiting this enzyme can reduce oxidative stress, stabilize neurotransmitter levels, and alleviate symptoms. In this context, a pharmacophoric model was created using PharmaGist with 31 hits extracted from BindingDB to enable a pharmacophoric-based search of potential MAO-B inhibitors in ZincPharmer’s chemical space, followed by the building of 10 conformers for each molecule in the software OMEGA, screening for structural and electrostatic similarity to safinamide using ROCS (Rapid overlay of chemical structures) and EON (Electrostatic similarity for lead-hopping), respectively. In addition, the molecular docking with Gold using the score function was performed to rank the ligands with the highest probabilities of affinity to MAO-B and then discriminate those with suitable physical chemical, pharmacokinetic, and toxicological features using the tools QikProp, SwissADME, and DEREK. Four potential ligands with selective MAO-B inhibitor properties were identified, which show promise as future therapeutic agents for MAO-B-related disorders. Worldwide schizophrenia depression diseases MAOB MAO (MAO-B brain stress levels symptoms context 3 pharmacophoricbased based ZincPharmers ZincPharmer s space 1 OMEGA Rapid structures Electrostatic leadhopping, leadhopping lead hopping , lead-hopping) respectively addition pharmacokinetic QikProp SwissADME DEREK identified MAOBrelated related disorders lead-hopping

The in silico study aimed to suggest phytochemicals from Commiphora leptophloeos leaves essential oil as therapies against coronavirus disease (COVID-19) (or severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). For that, we used molecular docking (MD), absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and pharmacokinetic analysis. MD showed the presence of hydrophobic and hydrogen bonds for nine compounds. β-Selinene and bicyclogermacrene showed the best interaction values with the protein Mpro (ID: 6Y2F) (-5.9) and chimeric receptor complexed with its receptor human ACE2 (ID: 6VW1) (-6.1 and -5.5) proteins, as well as low gastrointestinal and high epithelial absorptions, medium permeability for Caco-2 cells and high epithelial permeability, low oral excretion, and were inhibitors of CYP2C19 and CYP2C9 enzymes. On the other hand, both were not permeable to the blood-brain barrier and inhibitors or substrates for glycoprotein-D, and showed carcinogenic potential, but only β-selinene was considered mutagenic. Although little bioavailable, both presented aspects structurally adequate, being compounds with moderate synthesis difficulty. Therefore, more analyses are necessary to evaluate the mechanism of action and unsatisfactory parameters foreseen in bioinformatic assays. COVID19 COVID 19 (COVID-19 2 SARSCoV2. SARSCoV2 SARSCoV SARS CoV . SARS-CoV-2) that MD, , (MD) absorption distribution metabolism excretion ADMET (ADMET analysis βSelinene β Selinene ID (ID 6Y2F YF Y F 5.9 59 5 9 (-5.9 ACE 6VW1 VW 6.1 61 6 1 (-6. 5.5 55 -5.5 proteins absorptions Caco2 Caco Caco- CYPC CYP C CYP2C1 CYP2C enzymes hand bloodbrain blood brain glycoproteinD, glycoproteinD glycoprotein D, D glycoprotein-D potential βselinene selinene mutagenic bioavailable adequate difficulty Therefore assays COVID1 (COVID-1 SARS-CoV-2 (MD 5. (-5. 6VW 6. (-6 -5. (COVID- SARS-CoV- (-5 (- -5 (COVID SARS-CoV ( -

ABSTRACT: The study was conducted on a 3-year-old female Santa Inês sheep from a property located in the municipality of Santo Antônio de Tauá, west of Pará. The affected animal had a history of exophthalmos in the left eye, nasal discharge, and breathing difficulty for more than three months. On physical examination, the animal had a low body score, apathy, unilateral facial asymmetry, moderate unilateral left exophthalmos, mixed dyspnea and unilateral profuse serosanguinous nasal discharge. At necropsy, a large nasal mass was observed, predominantly yellowish-white with blackish-red areas, with an irregular, finely granular, moist, and friable surface. The mass invaded from the mucocutaneous junction of the left nostril to the choanae, infiltrated the frontal sinuses, the cribiform plate, and reached the meninges and the frontal portion of the brain. Microscopy of the surface of the nasal epithelium showed severe destruction of the turbinates and epithelia, evidenced by extensive areas of necrosis with a large amount of cellular debris, ulceration, and secondary bacterial infection. In the central nervous system there was pyogranulomatous meningitis with marked vessel congestion, as well as foci of necrosis and granulomatous inflammation. Immunohistochemistry showed intense staining of numerous intralesional hyphae for antibodies against Conidiobolus lamprauges. The diagnosis of granulomatous rhinitis of mycotic origin associated with the Conidiobolus lamprauges was based on epidemiological, clinical-pathological, and immunohistochemical data. ABSTRACT 3yearold yearold 3 year old Tauá Pará eye discharge months examination score apathy asymmetry necropsy observed yellowishwhite yellowish white blackishred blackish red irregular granular moist choanae sinuses plate brain epithelia debris ulceration infection congestion inflammation epidemiological clinicalpathological, clinicalpathological clinical pathological, pathological clinical-pathological data

RESUMO: O estudo foi realizado em um ovino, fêmea, de três anos de idade, da raça santa inês, procedente de uma propriedade localizada do município de Santo Antônio de Tauá, oeste do Pará. O animal acometido tinha histórico de exoftalmia no olho esquerdo, secreção nasal e dificuldade respiratória há mais de três meses. Ao exame físico o animal apresentava baixo escore corporal, apatia, assimetria facial unilateral, moderada exoftalmia unilateral esquerda, dispneia mista e exsudação nasal serossanguinolenta profusa unilateral. À necropsia, foi observada grande massa nasal, predominantemente branco-amarelada com áreas vermelho enegrecidas, de superfície irregular, finamente granular, úmida e friável. A massa invadia desde a junção mucocutânea do nariz esquerdo até as coanas, se infiltrava pelos seios nasais frontais, placa cribiforme e alcançava as meninges e a porção frontal do cérebro. À microscopia da superfície do epitélio nasal notou-se severa destruição dos cornetos e dos epitélios, evidenciada por extensas áreas de necrose com muitos debris celulares, ulceração e infecção bacteriana secundária. No sistema nervoso central (SNC) havia meningite piogranulomatosa com acentuada congestão de vasos, focos de necrose e inflamação granulomatosa. O diagnóstico de rinite granulomatosa de origem micótica associada ao fungo Conidiobolus lamprauges foi baseado nos achados da imuno-histoquímica. RESUMO ovino fêmea idade inês Tauá Pará meses corporal apatia esquerda necropsia brancoamarelada branco amarelada enegrecidas irregular granular friável coanas frontais cérebro notouse notou epitélios celulares secundária SNC (SNC vasos imunohistoquímica. imunohistoquímica imuno histoquímica. histoquímica imuno-histoquímica

This study details the preparation, antileishmanial assay, and in silico analysis of twenty 2-hydroxy-3-(1,2,3-triazolyl)propyl vanillin derivatives. These compounds were synthesized in three steps and evaluated against Leishmania infantum, Leishmania amazonensis, and Leishmania braziliensis promastigotes. Compounds 3s and 3t were the most effective, showing good activity against all Leishmania species tested. Molecular docking indicated that all compounds bind favorably to the sterol 14α-demethylase (CYP51) enzyme from L. infantum. ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicated good oral bioavailability, non blood-brain barrier penetration, and high gastrointestinal absorption. Posaconazole and compounds 3e, 3s, and 3t remained stable in the CYP51 binding region during 100 ns molecular dynamics (MD) simulations. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) analyses from the MD trajectory revealed significant conformational fluctuations of the CYP51 N-terminal, suggesting occasional expulsion of 3e, potentially explaining its higher IC50 (half-maximal inhibitory concentration) values. Pairwise decomposition analyses from molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations highlighted the importance of hydrophobic residues in interacting with the synthesized derivatives. preparation assay 2hydroxy31,2,3triazolylpropyl 2hydroxy3123triazolylpropyl hydroxytriazolylpropyl 2 hydroxy 3 1,2,3 triazolyl propyl 1 derivatives infantum amazonensis promastigotes s t effective tested 14αdemethylase αdemethylase 14α demethylase α CYP (CYP51 L absorption, absorption (absorption distribution metabolism toxicity bioavailability bloodbrain blood brain penetration 3e e CYP5 10 (MD simulations RMSD (RMSD RMSF (RMSF Nterminal, Nterminal N terminal, terminal N-terminal IC IC5 halfmaximal half maximal concentration values PoissonBoltzmann Poisson Boltzmann MM/PBSA MMPBSA MM PBSA (MM/PBSA 2hydroxy31 3triazolylpropyl triazolylpropyl 123 1,2, (CYP5 2hydroxy3 12 1,2 (CYP 2hydroxy 1,

Abstract It is known that neuronal maturation after birth lasts approximately twenty years and requires a large amount of energy. If a pregnancy occurs before maturation, the energy must be distributed between the mother and the offspring, having an effect on the anatomical and functional processes of the brain. Therefore, the electrical activity of the frontal cortex was compared, as well as the performance of its functions and maternal care in adolescents and young people (less than six months after giving birth). The NEUROPSI test (attention and coding) and a maternal care instrument were applied to primiparous adolescents and young people; electroencephalographic recordings were performed on a sample of this population. Significant differences are observed in the coding and attention processes (F= 4.5, α= 0.03*; F= 79.7, α= 0.00**), and a significant correlation between attention and maternal care (health and affection categories) as well as health care coding. The electrical activity of the frontal lobe was slower in primiparous adolescents as well as maternal care behaviors. The above is related to delay in the neuronal maturation of adolescent mothers.

Resumen Se sabe que la maduración neuronal tras el nacimiento dura aproximadamente veinte años y necesita gran cantidad de energía. Si ocurre un embarazo antes de la maduración, la energía debe repartirse entre la madre y la cría, teniendo efecto en los procesos anatómicos y funcionales del cerebro. Por ello, se comparó la actividad eléctrica de la corteza frontal, así como el desempeño de sus funciones y cuidados maternales en adolescentes y jóvenes (con menos de seis meses posteriores al parto). Se aplicó el test NEUROPSI (atención y codificación) y un instrumento de cuidados maternales a primíparas adolescentes y jóvenes; a una muestra de esta población se les realizó registros electroencefalográficos. Se observan diferencias significativas en los procesos de codificación y atención (F= 4.5, α= 0.03*; F=79.7, α= 0.00**), y una correlación significativa entre la atención y el cuidado maternal (categorías de salud y cariño), así como de la codificación sobre el cuidado de la salud. La actividad eléctrica del lóbulo frontal fue más lenta en las adolescentes primíparas, así como las conductas de cuidado maternal. Lo anterior se relaciona con una menor maduración neuronal de madres adolescentes.

Resumo: Introdução: A hipertensão arterial (HA) é a principal causa de morte por doenças cardiovasculares. Apesar dos avanços, o percentual de hipertensos não diagnosticados e não tratados é de 58,4%. A avaliação do dano cognitivo na hipertensão concentra-se na prevenção do acidente vascular cerebral, enquanto o dano funcional é ignorado. Esse manejo inadequado pode ser multifatorial. É objetivo fue analisar a opinião dos médicos sobre a relação entre hipertensão arterial e danos cognitivos. Metodologia: Estudo observacional, descritivo, transversal desenvolvido no período entre agosto de 2020 e agosto de 2023. Análise de dados obtidos a partir de questionário autoaplicável, anônimo e voluntário. Revelar informações sobre o perfil profissional, conhecimento sobre a HA, sua ligação com o comprometimento cognitivo (DC), diagnóstico e tratamento. Resultados: Foram incluídos 222 profissionais, 215 (96,8%) concordam com a existência de ligação entre hipertensão e outros fatores de risco cardiovascular na DC e 218 (98,1%) reconhecem ajudar pacientes com risco de sofrer de D.C. A avaliação da DC é realizada em casos selecionados por 132 (59,4%) participantes e 59 (26,7%) a fazem sempre. Dos que realizam avaliação, 103 (54%) utilizam o Mini Exame do Estado Mental (MEEM), 10 (5,2%) utilizam a Avaliação Cognitiva de Montreal (MoCA) e 9 (4,7%) utilizam o Clock Drawing Test. Em relação à diminuição da pressão arterial em pacientes idosos e a ligação com o risco de DC: 54 (24,3%) não reconhecem risco e 65 (29,2%) reconhecem risco moderado-alto. Em referência à implicação do tratamento de doenças cardiovasculares e DC: 217 (97,7%) reconheceram o efeito benéfico. Discussão: Dado o reconhecimento da ligação entre hipertensão e DC, seria de esperar que a DC fosse investigada na grande maioria, no entanto apenas 26,7% sempre a avaliam. Não há consenso sobre o método, sendo o MEEM o mais utilizado, com baixa aplicação do teste MoCA e/ou Clock Drawing Test, sendo estes últimos os que avaliam a função executiva, majoritariamente alterada nos DC vinculados à HA. Embora o tratamento das doenças cardiovasculares seja reconhecido como benéfico em relação à DC, o controle da HA em idosos é considerado arriscado. É feito um diagnóstico de uma situação em que é evidente uma disparidade entre o que se reconhece como saber e o que se afirma fazer. Conclusões: O papel da doença vascular no dano cerebral funcional é reconhecido, considerando-se necessário conhecer o estado cognitivo dos pacientes, porém há baixa aplicação de testes de triagem que avaliam a função executiva. Nesse contexto, evidencia-se uma lacuna entre o conhecimento e a prática médica.

Abstract: Introduction: High blood pressure (HBP) is the leading cause of death from cardiovascular disease. Despite the advances, the percentage of undiagnosed and untreated hypertensive patients is 58.4%. The evaluation of cognitive damage in HBP focuses on preventing stroke, while functional damage is ignored. This inadequate management may be multifactorial. The objective was to analyze the opinions that doctors have about the relationship between high blood pressure and cognitive damage. Methodology: Observational, descriptive, cross-sectional study developed in the period between August 2020 and August 2023. Analysis of data obtained from a self-administered, anonymous and voluntary questionnaire. Revealing information on the professional profile, knowledge of HBP, its link with cognitive impairment (CD), diagnosis and treatment. Results: 222 professionals were included, 215 (96.8%) agree with the existence of a link between HBP and other cardiovascular risk factors in CD, and 218 (98.1%) acknowledge assisting patients at risk of suffering from CD. The CD evaluation is carried out in selected cases by 132 (59.4%) participants and 59 (26.7%) always do it. Of those who perform evaluation, 103 (54%) use the Mini Mental State Examination (MMSE), 10 (5.2%) use the Montreal Cognitive Assessment (MoCA) and 9 (4.7%) use the Clock Drawing Test. Regarding the decrease in blood pressure in elderly patients and the link with risk of CD: 54 (24.3%) do not recognize risk and 65 (29.2%) recognize a moderate-high risk. In reference to the implication of the treatment of cardiovascular disease and CD: 217 (97.7%) recognized a beneficial effect. Discussion: Given the recognition of the link between HBP and CD, it would be expected that CD would be investigated in the vast majority, however only 26.7% always evaluate it. There is no consensus on the method, the MMSE being the most used, with a low application of the MoCA test and/or Clock Drawing Test, the latter being the ones that evaluate executive function, mostly altered in CD linked to HBP. Although the treatment of cardiovascular disease is recognized as beneficial with respect to CD, the control of HBP in older adults is considered risky. A diagnosis is made of a situation where a disparity is evident between what one recognizes as knowing and what one claims to do. Conclusions: The role of vascular disease in functional brain damage is recognized, considering it necessary to know the cognitive status of patients, however there is a low application of screening tests that evaluate executive function. In this context, a gap between medical knowledge and practice is shown.

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Resumo: A encefalopatia hepática consiste na disfunção ou deterioração cerebral, consequente a condições como a insuficiência hepática e a hipertensão portal, e é classificada no domínio médico como uma complicação clínica grave associada a lesões hepáticas graves. Foi efectuado um estudo de revisão sistemática qualitativa aplicando a declaração PRISMA 2020, utilizando os documentos disponíveis nas diferentes bases de dados e operadores booleanos para a pesquisa. A partir dos documentos selecionados, foi possível obter 840 referências de informação numa primeira pesquisa nas bases de dados e 8 registros de dados. Por fim, obteve-se um total de 16 fontes bibliográficas para a investigação. A encefalopatia hepática é uma síndrome neuropsiquiátrica que inclui comprometimento psicomotor e/ou sensorial, desorientação, incoordenação, comprometimento da memória, confusão, sonolência, estupor e coma, e existem várias ferramentas para o diagnóstico no primeiro nível de cuidados, Um dos principais instrumentos é a anamnese e o exame físico do doente, onde se esperam encontrar achados cognitivos e neuromusculares relacionados com a doença hepática grave. Os estudos complementares incluem testes laboratoriais, os critérios de West Haven, testes psicométricos, testes neurofisiológicos e estudos de neuroimagem, como a ressonância magnética.

Resumen: La encefalopatía hepática consiste en la disfunción o deterioro cerebral, consecuente a afecciones como insuficiencia hepática e hipertensión portal, en el ámbito médico es catalogada como una grave complicación clínica asociada al daño hepático severo. Se llevó a cabo un estudio cualitativo de revisión sistemática aplicando la declaración PRISMA 2020, en donde se utilizó los documentos disponibles en las diferentes bases de datos y con la aplicación de los operadores booleanos para su búsqueda. De los documentos seleccionados se pudieron obtener 840 referencias de información en una primera búsqueda en las bases de datos y 8 registros de datos. Finalmente, para la investigación se consiguió un total de 16 fuentes bibliográficas. La encefalopatía hepática se compone de un síndrome neuro-psiquiátrico que incluye deterioro psicomotor y/o sensitivo, desorientación, incoordinación, alteración de la memoria, confusión, somnolencia, estupor y coma, existen diversas herramientas para el diagnóstico desde el primer nivel de atención, una de las principales es la anamnesis y la exploración física del paciente donde se espera encontrar hallazgos cognitivos y neuromusculares relacionados a la enfermedad hepática grave, entre los estudios complementarios se emplea principalmente exámenes de laboratorio, Criterios de West Haven, prueba psicométrica, prueba neurofisiológica y estudios de neuroimagen como resonancia magnética.

Abstract: Hepatic encephalopathy consists of brain dysfunction or deterioration, consequent to conditions such as hepatic insufficiency and portal hypertension, and in the medical field it is cataloged as a serious clinical complication associated with severe liver damage. A qualitative study of systematic review was carried out applying the PRISMA 2020 statement, using the documents available in the different databases and Boolean operators for the search. From the selected documents it was possible to obtain 840 references of information in a first search in the databases and 8 data records. Finally, a total of 16 bibliographic sources were obtained for the research. Hepatic encephalopathy is composed of a neuropsychiatric syndrome that includes psychomotor and/or sensory impairment, disorientation, incoordination, memory alteration, confusion, somnolence, stupor and coma, there are several tools for diagnosis from the first level of care, One of the main ones is the anamnesis and physical examination of the patient where it is expected to find cognitive and neuromuscular findings related to severe liver disease, among the complementary studies are mainly used laboratory tests, West Haven Criteria, psychometric test, neurophysiological test and neuroimaging studies such as magnetic resonance imaging.

SUMMARY: To explore morphological evidence for neuronal circuits between adenosine A2A receptor (A2AR) neurons in the nucleus accumbens (NAc) and orexin neurons. The utilized adeno-associated virus (AAV) encoding humanized Renilla green fluorescent protein (hrGFP) as a tracer to visualize the expression of the A2AR neurons in the NAc and their axon distributions in orexin neurons. The Cre-dependent AAV was injected into the NAc in adenosine A2AR-Cre mice. Immunohistochemistry was then used to visualize hrGFP and their projections in orexin neurons. The data revealed that NAc A2AR neurons, mainly expressed in γ-aminobutyric acidergic (GABAergic) projection neurons, projected to the hypothalamus, with apparent contacts of hrGFP containing boutons onto orexin-immunoreactive (IR) soma and dendrites. We also observed strong staining of orexin-IR varicose terminals in the NAc, with apparent contacts of orexin-IR terminals onto A2AR neurons. Furthermore, in the NAc, orexin-IR varicosities contained vesicular glutamate transporter 2 (VGluT2) and synaptophysin (Syp). These data provide morphological evidence for exploring the function between NAc A2AR neurons and orexin neuron in the hypothalamus, particularly in regulating sleep processes.

RESUMEN: El objetivo de este trabajo fue explorar la evidencia morfológica de los circuitos neuronales entre las neuronas del receptor de adenosina A2A (A2AR) en el núcleo accumbens (NAc) y las neuronas de orexina. El virus adenoasociado (AAV) que codifica la proteína fluorescente verde Renilla humanizada (hrGFP) se utilizó como trazador para visualizar la expresión de las neuronas A2AR en la NAc y sus distribuciones de axones en las neuronas de orexina. El AAV dependiente de Cre se inyectó en la NAc en ratones adenosina A2AR-Cre. Luego se utilizó inmunohistoquímica para visualizar hrGFP y sus proyecciones en las neuronas de orexina. Los datos revelaron que las neuronas NAc A2AR, expresadas principalmente en neuronas de proyección acidérgicas γ-aminobutíricas (GABAérgicas), se proyectaban hacia el hipotálamo, con contactos aparentes de botones que contenían hrGFP en el soma y las dendritas inmunorreactivas con orexina (IR). También observamos una fuerte tinción de las terminales varicosas de orexina-IR en la NAc, con contactos aparentes de las terminales de orexina-IR en las neuronas A2AR. Además, en la NAc, las varicosidades de orexina-IR contenían transportador vesicular de glutamato 2 (VGluT2) y sinaptofisina (Syp). Estos datos proporcionan evidencia morfológica para explorar la función entre las neuronas NAc A2AR y la neurona orexina en el hipotálamo, particularmente en la regulación de los procesos del sueño.

SUMMARY: Cerebral hemorrhage (CH) presents a significant risk for cognitive decline. Our research aimed to assess the impact of Apricot Kernel Oil (AKO) on cognitive function and inflammatory response in a hemorrhagic stroke model using Wistar rats, and to examine their correlation. Fifty Wistar rats were randomly assigned to five groups: a control group, an AKO supplemented group (receiving 400 mg/kg AKO), a CH group (with induced CH), and CH groups supplemented with 200 and 400 mg/kg AKO, each containing 10 rats. Cognitive function was evaluated using the Y-electric maze test across these groups. Additionally, enzyme-linked immunosorbent assay and real-time PCR were utilized to analyze the protein and gene expression profiles of inflammatory and apoptotic factors in the brain. Compared to the control group, rats in the CH group took longer to master the maze criteria (P<0.05). Moreover, the CH group exhibited significantly increased levels of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and decreased levels of anti-inflammatory cytokines IL-4 and IL-10 compared to the control group (P<0.05). Conversely, rats in the CH+400 mg/kg AKO group showed opposite trends in electrical simulation time, inflammatory factor protein, and gene expression profile (Bcl- 2, BAX, Caspase-3, and p53) compared to the CH group (P<0.05). Our findings suggest that AKO extract may ameliorate cognitive dysfunction following CH in rats, potentially through modulation of inflammatory factors secreted by microglia.

RESUMEN: La hemorragia cerebral (HC) presenta un riesgo significativo de deterioro cognitivo. Nuestra investigación tuvo como objetivo evaluar el impacto del aceite de semilla de albaricoque (ASA) en la función cognitiva y la respuesta inflamatoria en un modelo de accidente cerebrovascular hemorrágico utilizando ratas Wistar, y examinar su correlación. Se asignaron aleatoriamente cincuenta ratas Wistar a cinco grupos: un grupo control, un grupo suplementado con ASA (que recibió 400 mg/kg de ASA), un grupo HC (con HC inducido) y grupos HC suplementados con 200 y 400 mg/kg de ASA, cada uno. La función cognitiva se evaluó mediante la prueba del laberinto eléctrico Y en estos grupos. Además, se utilizaron un ensayo inmunoabsorbente ligado a enzimas y una PCR en tiempo real para analizar los perfiles de expresión de proteínas y genes de factores inflamatorios y apoptóticos en el cerebro. En comparación con el grupo de control, las ratas del grupo HC tardaron más en dominar los criterios del laberinto (P<0,05). Además, el grupo HC exhibió niveles significativamente mayores de citocinas proinflamatorias interleucina-1β (IL-1β), IL-6 y factor de necrosis tumoral- α, y niveles reducidos de citocinas antiinflamatorias IL-4 e IL-10 en comparación al grupo control (P<0,05). Por el contrario, las ratas del grupo HC+400 mg/kg ASA mostraron tendencias opuestas en el tiempo de simulación eléctrica, la proteína del factor inflamatorio y el perfil de expresión génica (Bcl-2, BAX, Caspasa-3 y p53) en comparación con el grupo HC (P <0,05). Nuestros hallazgos sugieren que el extracto de ASA puede mejorar la disfunción cognitiva después de la HC en ratas, potencialmente mediante la modulación de factores inflamatorios secretados por la microglia.

SUMMARY: There exists a scarcity of neurocognitive research that has successfully used electrophysiology as an objective tool to assess different learning modalitiesthat are commonly used in anatomy. The objective of this study was to explore the trend in the expression of brain waves in medical students when using different didactic strategies in learning anatomy. An exploratory, observational, cross-sectional study was conducted on 22 first- semester medical students in anatomy. Using didactic strategies with different pedagogical tools such as biological models (human skulls and pig hearts) and/or digital application (Visible Body software), and different evaluation methods, students were grouped into three groups: "EOR1" students who learned using a skull and were evaluated with it; "EOV1" students who learned using a pig heart and were evaluated with the Visible Body software; and "EOV2" for students who learned through the Visible Body software and were evaluated with it. During the evaluation, each student was monitored in real-time using an electroencephalogram and the Emotiv EPOC brain-computer interface system to record the electro-physiological activity of beta (B), theta (T), and gamma (G) waves. The data obtained (the trend of the electrical activity of each wave and its relationship with students' performance in each didactic strategy) were analyzed using Pearson's correlation coefficient. Groups EOR1 and EOV1 had satisfactory results in their evaluations and showed a predominance of B waves (x=67.33) and T waves (x=57.67). Additionally, a strongly positive correlation (r=0.82) was found between the presence of B waves and the duration of T waves. Students who used three-dimensional biological models as a pedagogical tool showed a predominance of B and T waves, which are associated with sensorimotor and exploratory learning necessary for studying anatomy.

RESUMEN: Son escasos los estudios de neurociencia cognitiva que permitan comprender, de manera objetiva, las manifestaciones electrofisiológicas de los estudiantes de medicina expuestos a diferentes herramientas pedagógicas utilizadas en el área de anatomía. El objetivo de este trabajo fue explorar la tendencia en la expresión de las ondas cerebrales de estudiantes de medicina, al utilizar diferentes estrategias didácticas en el aprendizaje de la anatomía. Se realizó un estudio exploratorio, observacional, de corte transversal en 22 estudiantes de medicina de primer semestre en anatomía. Utilizando estrategias didácticas con diferentes herramientas pedagógicas; como modelos biológicos (cráneos humanos y corazones porcinos) y/o aplicación digital (software Visible Body (SVB)), y diferente método de evaluación, se agruparon los estudiantes en tres grupos: “EOR1” estudiantes que aprendieron usando un cráneo y se evaluaron con este, “EOV1” estudiantes que aprendieron usando un corazón porcino y fueron evaluados con el SVB, y “EOV2” para los estudiantes que aprendieron a través del SVB y fueron evaluados con este. Durante la evaluación, cada estudiante fue monitorizado en tiempo real, utilizando un electroencefalograma y el sistema interfaz cerebro - computadora Emotiv EPOC para registrar la actividad electrofisiológica de las ondas beta (B), theta (T) y gamma (G). Los datos obtenidos (tendencia de la actividad eléctrica de cada onda y su relación con el desempeño de los estudiantes en cada estrategia didáctica) fueron analizados usando el índice de correlación de Pearson. Los grupos EOR1 y EOV1, tuvieron resultados satisfactorios en sus evaluaciones y presentaron predominio de ondas B (X=67,33) y T (X=57,67), además, se evidenció una correlación fuertemente positiva (r=0,82) entre la presencia de B y el tiempo de permanencia de T. Los estudiantes que utilizaron modelos biológicos tridimensionales como herramienta pedagógica presentaron predominio de las ondas B y T, asociadas con aprendizajes sensoriomotores y de tipo exploratorio necesarios para el estudio en anatomía.

SUMMARY: Formaldehyde induces oxidative damage in hippocampal tissue and blood serum by suppressing antioxidant defenses and increasing lipid peroxidation. This results in damage to DNA, proteins, and lipids within cells, disrupting neuronal functions, and may even lead to cell death (apoptosis). Apoptosis occurs as a cellular response triggered by formaldehyde through various mechanisms, including mitochondrial dysfunction, oxidative stress, and DNA damage. Arbutus unedo L. (AUL), which is rich in antioxidants, represents a potential countermeasure. The aim of our study is to investigate the immunohistochemical and biochemical effects of AUL fruit extract (AUE) on apoptosis and oxidative stress induced by FA exposure in the rat hippocampus. The rats were divided into four groups: the experimental group (EG) received 20 mg/kg AUE by oral gavage and 10 ppm FA inhalation; the formaldehyde group (FG) received 10 ppm FA inhalation only; the sham group (SG) received 10 mg/kg AUE by oral gavage; and the control group (CG) underwent routine observation. Hippocampal tissue was isolated after blood sampling. A number of physical changes, such as yellowing of feathers and tail spots, were observed in FA-exposed groups. The biochemical analysis showed significant differences in brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), GSH (Glutathione) and nitric oxide (NO) levels between the groups. The AUE-treated groups had reduced MDA levels, suggesting a potential reduction in oxidative stress, along with lower apoptotic cell rates in caspase-3 assessments. The FG rats had lower BDNF levels than CG. The SG had the fewest apoptotic cells. All these findings indicate AUE's potential to mitigate neuron damage and reduce oxidative stress.

RESUMEN: El formaldehído induce daño oxidativo en el tejido del hipocampo y del plasma sanguíneo al suprimir las defensas antioxidantes y aumentar la peroxidación lipídica. Esto provoca daños en el ADN, las proteínas y los lípidos dentro de las células, alterando las funciones neuronales e incluso puede provocar la muerte celular (apoptosis). La apoptosis se produce como una respuesta celular desencadenada por el formaldehído a través de diversos mecanismos, incluida la disfunción mitocondrial, el estrés oxidativo y el daño del ADN. Arbutus unedo L. (AUL), rico en antioxidantes, representa una posible contramedida. El objetivo de nuestro estudio fue investigar los efectos inmunohistoquímicos y bioquímicos del extracto de fruta AUL (AUE) sobre la apoptosis y el estrés oxidativo inducido por la exposición a FA en el hipocampo de rata. Las ratas se dividieron en cuatro grupos: el grupo experimental (GE) recibió 20 mg/kg de AUE por sonda oral y 10 ppm de FA por inhalación; el grupo de formaldehído (GF) recibió sólo una inhalación de 10 ppm de FA; el grupo simulado (GS) recibió 10 mg/kg de AUE mediante sonda oral; y el grupo control (GC) se sometió a observación de rutina. Se aisló tejido del hipocampo después de una muestra de sangre. En los grupos expuestos a FA se observaron una serie de cambios físicos, como coloración amarillenta del pelaje y manchas en la cola. El análisis bioquímico mostró diferencias significativas en los niveles de factor neurotrófico derivado del cerebro (BDNF), malondialdehído (MDA), GSH (glutatión) y óxido nítrico (NO) entre los grupos. Los grupos tratados con AUE tenían niveles reducidos de MDA, lo que sugiere una reducción potencial del estrés oxidativo, junto con tasas de células apoptóticas más bajas en las evaluaciones de caspasa-3. Las ratas GF tenían niveles de BDNF más bajos que GC. El GS tenía la menor cantidad de células apoptóticas. Todos estos hallazgos indican el potencial del AUE para mitigar el daño neuronal y reducir el estrés oxidativo.

SUMMARY: The hypothalamic peptide orexin has a prominent role in arousal-related processes. Parvalbumin (PV) positive neurons, as one of the most important subtypes of γ-aminobutyric acid (GABA) interneurons, which also participate in sleep-wake regulation. To broaden the understanding of the neural control and connection between these two types of neurons in the sleep associated nuclei, a double-label immunohistochemical method was used to investigate the overlap between PV immunopositive distributions and projections of orexin neurons in mouse brain. In the basal forebrain, overlap was observed in the nucleus accumbens shell (AcbSh), the nucleus of the horizontal limb of the diagonal band (HDB), magnocellular preoptic nucleus (MCPO), substantia innominata (SI), but avoided the nucleus accumbens core (AcbC). In the diencephalon, this dual innervation extended in the direction near the edge of the 3rd ventricle (3V) to the ventrolateral preoptic nucleus (VLPO), although the density of PV neurons there was somewhat lighter. Orexin immunoreactive neurons in several lateral hypothalamic areas (LH) were embedded within dense clusters of PV processes when the buttons of orexin were in obvious contact with PV immunoreactivity. In the remainder of hypothalamus, mainly including the ventral tuberomammillary nucleus (VTM), there were few fine orexin fibers and buttons contact with PV soma. Intermingled orexin and PV immunoreactivity were observed in the ventral tegmental area (VTA), and sparse overlap was observed in the ventrolateral periaqueductal gray (VLPAG) and laterodorsal tegmental nucleus (LDT) in the brainstem. Thus, these two different types of neurons, originating in different parts of the brain, together target several brain regions and brainstem monoaminergic nuclei involved in the roles of motivation, stress, locomotion, especially in the regulation of sleep.

RESUMEN: El péptido hipotalámico orexina tiene un papel destacado en los procesos relacionados con la excitación. Neuronas positivas para parvalbúmina (PV), como uno de los subtipos más importantes de interneuronas de ácido g-aminobutírico (GABA), que también participan en la regulación del sueño-vigilia. Para ampliar la comprensión del control neuronal y la conexión entre estos dos tipos de neuronas en los núcleos asociados al sueño, se utilizó un método inmunohistoquímico de doble marcado para investigar la superposición entre las distribuciones inmunopositivas de PV y las proyecciones de las neuronas de orexina en el cerebro de un ratón. En el prosencéfalo basal, se observó superposición en la capa del núcleo accumbens (AcbSh), el núcleo de la rama horizontal de la banda diagonal (HDB), el núcleo preóptico magnocelular (MCPO), la sustancia innominada (SI), pero se evitó el núcleo del núcleo accumbens. (AcbC). En el diencéfalo, esta inervación dual se extendía en dirección cercana al margen del tercer ventrículo (3V) hasta el núcleo preóptico ventrolateral (VLPO), aunque la densidad de neuronas PV allí era algo más ligera. Las neuronas inmunorreactivas de orexina en varias áreas hipotalámicas laterales (LH) estaban incrustadas dentro de densos grupos de procesos PV cuando los botones de orexina estaban en contacto obvio con la inmunorreactividad de PV. En el resto del hipotálamo, incluido principalmente el núcleo tuberomamilar ventral (VTM), había pocas fibras finas de orexina y botones en contacto con el soma PV. Se observó inmunorreactividad de orexina y PV entremezcladas en el área tegmental ventral (VTA), y se observó una escasa superposición en el núcleo gris periacueductal ventrolateral (VLPAG) y el núcleo tegmental laterodorsal (LDT) en el tronco encefálico. Así, estos dos tipos diferentes de neuronas, que se originan en diferentes partes del cerebro, se dirigen juntas a varias regiones del cerebro y a núcleos monoaminérgicos del tronco encefálico implicados en las funciones de motivación, estrés, locomoción y especialmente en la regulación del sueño.

SUMMARY: Because horned animals are prone to conflict, they may have a higher risk of developing a brain contusion as a result of a horn strike. Repeated brain trauma can affect the hippocampus, which is involved in memory and orientation. The aim of this study was to histopathologically examine the blood-brain barrier (BBB) of the hippocampus in horned and hornless female sheep. Skulls of 4 horned and 6 hornless female sheep aged 16±4 months were obtained from the abattoir. Brains were carefully removed and preserved in 10 % formalin for 5 days. Sections were taken from bilateral hippocampus. Specimens were stained with hematoxylin-eosin (H&E) and Tunel methods, and the histopathologic structures of the BBB were examined by light microscopy. BBB damage scores evaluated. The results were analyzed by Mann-Whitney U test. The BBB damage score was found to be higher in horned female sheep. Astrocytes was more branching and BBB was more intact in hornless female sheep. This is considered that more astrocyte branches may play an important role in the protective mechanism. The difference in intracerebral defense mechanism against brain trauma in female sheep may serve as a model for investigating molecular mechanisms. The impairment of the BBB in the hippocampal region of horned female sheep may result in their memory, intelligence, and navigational abilities being lower than those of hornless female sheep. This could open the horizon for better advances in human and animal brain health.

RESUMEN: Debido a que los animales con cuernos son propensos a los conflictos, pueden tener un mayor riesgo de desarrollar una contusión cerebral como resultado de un golpe con un cuerno. Los traumatismos cerebrales reiterados pueden afectar el hipocampo relacionado con la memoria y la orientación. El objetivo de este estudio fue examinar histopatológicamente la barrera hematoencefálica (BHE) del hipocampo en ovejas con y sin cuernos. Se obtuvieron de un matadero los cráneos de 4 ovejas con cuernos y 6 sin cuernos de 16 ± 4 meses de edad. Los cerebros se extrajeron cuidadosamente y se conservaron en formalina al 10 % durante 5 días. Se tomaron secciones del hipocampo bilateral. Las muestras se tiñeron con hematoxilina-eosina (H&E) y métodos Tunel, y las estructuras histopatológicas de la BHE se examinaron mediante microscopía óptica. Se evaluaron las puntuaciones de daño de la BHE. Los resultados fueron analizados mediante la prueba U de Mann-Whitney. Se descubrió que la puntuación de daño de la BHE era mayor en las ovejas con cuernos. Los astrocitos estaban más ramificados y la BHE estaba más intacta en las ovejas sin cuernos. Se considera que más ramas de astrocitos pueden desempeñar un papel importante en el mecanismo de protección. La diferencia en el mecanismo de defensa intracerebral contra el trauma cerebral en las ovejas puede servir como modelo para investigar los mecanismos moleculares. El deterioro de la BHE en la región del hipocampo de las ovejas con cuernos puede provocar que su memoria, inteligencia y capacidades de orientación sean inferiores a las de las ovejas sin cuernos. Esto podría abrir el horizonte para mejores avances en la salud del cerebro humano y animal.

SUMMARY: In current study, we used Nissl staining to examine the histological structure of the juvenile Chinese alligator brain, and immunohistochemistry (IHC) staining to detail the serotonin (5-hydroxytryptamine, 5-HT) localization and morphology of neurons belonging to the serotonergic system. Nissl staining revealed that the Chinese alligator brain was divided into four regions (telencephalon, diencephalon, brainstem, and cerebellum) and a connected ventricular system (containing the pair of lateral ventricles, third ventricle, fourth ventricle and the aqueduct). According to the IHC results, 5-HT immunoreactive (5-HT-IR) neurons were primarily observed in the cerebral cortex, the hypothalamic paraventricular nucleus (PH), tectum and tegmentum of the optic lobes, the medial longitudinal fasciculus (Flm) of medulla oblongata and the cerebellar cortex. 5-HT-IR fibers were mostly located lateral to the hypothalamic paraventricular nucleus (PH), in the medial vestibular nucleus (MVe) of the medulla oblongata, and in the choroid plexus (CP) of the lateral ventricles. Additionally, our findings paralleled those results of other reptiles; nevertheless, some distinctions in terms of both histological architecture and function were identified. The layering of the cerebral cortex and tectum, as well as the arrangement of Purkinje cells, differed between reptile brains. The distribution of 5-HT-IR neurons varied in the layer of cerebral and cerebellar cortex when compared to other reptiles. Within the diencephalon, 5-HT-IR neurons formed distinct nuclei in the hypothalamic paraventricular nucleus (PH), but few in the infundibular recess.

RESUMEN: Utilizamos la tinción de Nissl para examinar la estructura histológica del cerebro juvenil del caimán chino y la tinción inmunohistoquímica (IHC) para detallar la localización y morfología de la serotonina (5-hidroxitriptamina, 5-HT) de las neuronas que pertenecen al sistema serotoninérgico. La tinción de Nissl reveló que el cerebro del caimán chino estaba dividido en cuatro regiones (telencéfalo, diencéfalo, tronco encefálico y cerebelo) y un sistema ventricular conectado (que contiene el par de ventrículos laterales, el tercer ventrículo, el cuarto ventrículo y el acueducto). Según los resultados de IHC, las neuronas inmunorreactivas 5-HT (5-HT-IR) se observaron principalmente en la corteza cerebral, el núcleo paraventricular (PH) hipotalámico, el tectum y tegmento de los lóbulos ópticos, el fascículo longitudinal medial (Flm) de médula oblonga y la corteza cerebelosa. Las fibras 5-HT-IR se ubicaron principalmente lateral al núcleo paraventricular (PH) hipotalámico, en el núcleo vestibular medial (MVe) de la médula oblonga y en el plexo coroideo (CP) de los ventrículos laterales. Además, nuestros hallazgos fueron semejantes a los resultados obtenidos de otros reptiles; sin embargo, se identificaron algunas distinciones en términos tanto de arquitectura histológica como de función. Las capas de la corteza cerebral y el tectum, así como la disposición de las neuronas purkinjenses, diferían entre los cerebros de los reptiles. La distribución de las neuronas 5-HT-IR varió en la capa de la corteza cerebral y cerebelosa en comparación con otros reptiles. Dentro del diencéfalo, las neuronas 5-HT-IR formaron núcleos distintos en el núcleo paraventricular (PH) hipotalámico, pero pocos en el receso infundibular.