Listeria monocytogenesy mecanismo de caballo de Troya a través de la barrera hematoencefálica / isteria monocytogenesand Trojan horse mechanism across the blood-brain barrier

Las infecciones del sistema nervioso central son potencialmente mortales, causadas por patógenos, como bacterias, virus y hongos. Para llegar hasta el cerebro, los microorganismos utilizan diversas vías y formas. Este patogeno es una bacteria grampositiva corta, flagelar e intracelular, con la capacidad de inducir su internalización en células fagocíticas (monocitos/macrófagos) y no fagocíticas (células endoteliales). Al infectar los macrófagos, estos microorganismos se valen de su capacidad de fijación, adhesión y migración transendotelial, para cruzar la barrera hematoencefálica, finalmente, generando meningitis bacteriana. En esta revisión describimos el mecanismo de caballo de Troya usado por Listeria monocytogenespara invadir el cerebro en el desarrollo de enfermedades infecciosas e incorporamos nuevos conocimientos sobre moléculas que intervienen en dicho mecanismo(AU)

Central nervous system infections are life-threatening, caused by pathogens such as bacteria, viruses and fungi. To access the brain, microorganisms use various mechanisms. Listeria monocytogenes is a short, flagellar and intracellular gram-positive bacterium, with the ability to induce its internalization in phagocytic (monocytes/macrophages) and non-phagocytic (endothelial cells) cells. By infecting macrophages, these microorganisms take advantage of their binding, adhesion, and transendothelial migrationcapacity to cross the blood-brain barrier, finally generating bacterial meningitis. In this review we describe the Trojan horse mechanism used by Listeria monocytogenesto invade the brain in the development of infectious diseases and we incorporate new knowledge about molecules that intervene in this mechanism(AU)

Dor neuropática: sentimentos e vivências de pacientes após lesões traumáticas / Neuropathic pain: feelings and experiences of patients after traumatic injuries / Dolor neuropático: sentimientos y experiencias de pacientes después lesiones traumáticas

Objetivo: Compreender o cotidiano de portadores de dor neuropática decorrente de lesão traumática. Metodologia: Pesquisa exploratória, descritiva, de abordagem qualitativa, com participantes selecionados por meio de mídias sociais. A coleta de dados foi realizada entre o período de julho a setembro de 2022, com indivíduos adultos que possuem diagnóstico de dor neuropática após lesão traumática. A coleta ocorreu por meio de um formulário online, utilizando um questionário sociodemográfico e um questionário aberto, para a captura de informações pertinentes sobre seu caso clínico e vivência com a dor crônica. Os dados foram analisados por meio de Bardin. Todos os preceitos éticos foram respeitados e o projeto foi aprovado sob parecer n.º 5.529.581 da Universidade Cesumar. Resultados: Participaram 15 pessoas com dor neuropática, com prevalência do sexo feminino (93,3%), com idade entre 41 a 50 anos (66,7%). Observou-se que 53,3% relataram comorbidades crônicas, sendo as doenças psíquicas, ansiolíticas e cardíacas mais citadas. Ainda, 33,3% dos participantes relataram que foram internados por causas de dores ou por tentativa de suicídio, 93,3% usam opióides e analgésicos potentes e ainda foram citados antidepressivos e ansiolíticos em 62% das respostas. Dentre os temas em destaque nas respostas, sobressaíram-se "Contexto e diagnóstico da dor neuropática; Vivência e frequência da dor; Apoio profissional e familiar diante da doença". Considerações Finais: Nesse sentido, a percepção acerca dos profissionais de saúde e valorização do médico para o tratamento da dor neuropática está relacionada, muitas vezes, à necessidade de aumentar o conhecimento referente ao manejo da dor e à utilização de opióides.

Objective: To understand the daily life of patients with neuropathic pain resulting from traumatic injury. Methodology: Exploratory, descriptive research, with a qualitative approach, with participants selected through social media. Data collection was carried out between July and September 2022, with adult individuals diagnosed with neuropathic pain after traumatic injury. The collection took place through an online form, using a sociodemographic questionnaire and an open questionnaire, to capture relevant information about their clinical case and experience with chronic pain. Data were analyzed using Bardin. All ethical precepts were respected and the project was approved by report n.º 5,529,581 of Cesumar University. Results: 15 people with neuropathic pain participated, with a prevalence of females (93.3%), aged between 41 and 50 years (66.7%). It was observed that 53.3% reported chronic comorbidities, with psychic, anxiolytic and cardiac diseases being the most cited. Also, 33.3% of the participants reported that they were hospitalized due to pain or a suicide attempt, 93.3% used opioids and potent analgesics, and antidepressants and anxiolytics were mentioned in 62% of the answers. Among the topics highlighted in the responses, the most important were "Context and diagnosis of neuropathic pain; Experience and frequency of pain; Professional and family support in the face of the disease". Final Considerations: In this sense, the perception of health professionals and the appreciation of physicians for the treatment of neuropathic pain is often related to the need to increase knowledge regarding pain management and the use of opioids.

Objetivo: Comprender el cotidiano de los pacientes con dolor neuropático resultante de lesiones traumáticas. Metodología: Investigación exploratoria, descriptiva, con enfoque cualitativo, con participantes seleccionados a través de las redes sociales. La recolección de datos se llevó a cabo entre julio y septiembre de 2022, con individuos adultos diagnosticados con dolor neuropático posterior a una lesión traumática. La recogida se realizó a través de un formulario online, utilizando un cuestionario sociodemográfico y un cuestionario abierto, para captar información relevante sobre su caso clínico y experiencia con el dolor crónico. Los datos se analizaron utilizando Bardin. Se respetaron todos los preceptos éticos y el proyecto fue aprobado bajo el dictamen número 5.529.581 de la Universidad Cesumar. Resultados: Participaron 15 personas con dolor neuropático, con predominio del sexo femenino (93,3%), con edades entre 41 y 50 años (66,7%). Se observó que 53,3% relataron comorbilidades crónicas, siendo las enfermedades psíquicas, ansiolíticas y cardíacas las más citadas. Aún así, el 33,3% de los participantes informaron que fueron hospitalizados por dolor o intento de suicidio, el 93,3% usaba opioides y analgésicos potentes, y los antidepresivos y ansiolíticos se mencionaron en el 62% de las respuestas. Entre los temas destacados en las respuestas, los más importantes fueron "Contexto y diagnóstico del dolor neuropático; Experiencia y frecuencia del dolor; Apoyo profesional y familiar ante la enfermedad". Consideraciones Finales: En este sentido, la percepción de los profesionales de la salud y la apreciación de los médicos por el tratamiento del dolor neuropático muchas veces se relaciona con la necesidad de aumentar el conocimiento sobre el manejo del dolor y el uso de opioides.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Primary somesthetic cortex involvement in fibromyalgia: review of neuroimage studies / Envolvimento do córtex somestésico primário na fibromialgia: revisão de estudos de neuroimagem

ABSTRACT BACKGROUND AND OBJECTIVES: The mechanisms underlying nociplastic pain, such as fibromyalgia (FM), are not fully understood, however, it is believed that altered sensory processing and pain modulation play prominent roles in the maintenance of nociplastic pain. The hypothesis is that changes in the primary somesthetic cortex (S1) contribute to the generalized pain character of FM. The objective of this study was to evaluate the involvement of the primary somesthetic cortex in humans with fibromyalgia, as well as to investigate possible associations between S1 changes and clinical signs and symptoms of FM. CONTENTS: For this integrative review, the following databases were used: Pubmed and Web of Science, including observational studies carried out in humans with FM. In total, 541 studies were identified and four were included. The majority of studies are case-control studies, published between 2016 and 2022. In total, data from 161 individuals were included in this review. It was identified that there are morphological changes, hyperactivation and increased functional connectivity between S1 and periaqueductal gray matter and between S1 and anterior cingulate cortex. CONCLUSION: Patients with FM present morphological changes and hyperactivation in S1, as well as increased functional connectivity between S1 and periaqueductal gray matter and S1 and limbic system. Furthermore, different bilateral somatotropic subregions (legs, chest, fingers, hands, face and back) showed reduced functional connectivity in patients with FM. These regions are often presented as "tender points" in FM.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os mecanismos subjacentes à dor nociplástica, como a fibromialgia (FM), não são totalmente compreendidos, contudo acredita-se que o processamento sensorial e a modulação da dor alterados desempenham papéis proeminentes para a manutenção da dor nociplástica. Com a hipótese de que alterações no córtex somestésico primário (S1) contribuam para o caráter de dor generalizada da FM, o objetivo deste estudo foi avaliar o envolvimento do córtex somestésico primário em humanos com FM, bem como investigar possíveis associações entre alterações de S1 com sinais e sintomas clínicos da FM. CONTEÚDO: Para esta revisão integrativa, foram utilizadas as seguintes bases de dados: Pubmed e Web of Science, incluindo estudos observacionais realizados em humanos com FM. No total, 541 estudos foram identificados e quatro foram incluídos. A maioria dos estudos são do tipo caso-controle, publicados entre 2016 e 2022. Ao todo, dados de 161 indivíduos foram incluídos. Foi identificado que há alterações morfológicas, hiperativação e aumento da conectividade funcional entre S1 e substância cinzenta periaquedutal e entre S1 e córtex cingulado anterior. CONCLUSÃO: Pacientes com FM apresentam alterações morfológicas e hiperativação em S1, bem como aumento da conectividade funcional entre S1 e substância cinzenta periaquedutal e S1 e sistema límbico. Ademais, diferentes sub-regiões somatotrópicas bilaterais (pernas, tórax, dedos, mãos, face e costas) apresentaram redução da conectividade funcional em pacientes com FM. Essas regiões são frequentemente apresentadas como "tender points" na FM.

Prevalence of brain fag syndrome and its correlation with stimulant use and socioeconomic/demographic characteristics among university undergraduate students in Nigeria

Background: Brain Fag Syndrome (BFS) is a culture-bound syndrome characterized by cognitive and somatic symptoms, commonly reported among African students. This study aimed to determine the prevalence of BFS among Nigerian university students and examine its associated factors. Methods: A cross-sectional survey was conducted among undergraduate students from a university in the northwest region of Nigeria. The study utilized a self-administered questionnaire to collect data on socio-demographic characteristics, stimulant use, course of study, and academic performance. The presence of BFS was assessed using standardized diagnostic criteria. Results:The study included a total of 625 participants, in their young adulthood. The prevalence of BFS among Nigerian university students was found to be 62.7%. The majority of affected students were aged 20-30, male, and from the Hausa ethnic group. No significant association was found between stimulant use and BFS. However, there was a significant relationship between the course of study and the occurrence of BFS. Academic performance (CGPA) showed a weak negative association with BFS. Other socio-demographic factors such as age, gender, ethnicity, relationship status, birth position, type of home, and family income did not predict the occurrence of BFS. Conclusion: The high prevalence highlights the need for attention to mental health issues among this population. The results emphasize the importance of considering the course of study and academic performance when studying BFS. Further research is warranted to explore the underlying mechanisms and develop effective interventions for students affected by BFS.

Apport de l'IRM multimodale dans la prise en charge des tumeurs encéphaliques chez l'adulte à Abidjan / Contribution of multimodal MRI in the management of brain tumors in adults in Abidjan

Dans le monde, le nombre de nouveaux cas de tumeurs encéphaliques était de 14 millions en 2014 avec environ 8 millions de personnes décédées. Objectif: déterminer l'efficacité diagnostique de l'IRM multimodale dans la prise en charge des tumeurs encéphaliques dans notre contexte. Matériels et Méthodes: Etude rétrospective à visée descriptive, multicentrique sur une période de 2 ans allant de février 2017 à mars 2019, dans 2 services de radiologie et 2 services de Neurochirurgie, à Abidjan. Nous nous sommes intéressés àtous les patients ayant réalisé une IRM multimodale pour suspicion d'un processus tumoral encéphalique, et qui ont eu une exérèse chirurgicale suivie d'un examen anatomopathologique de la pièce opératoire. Les examens d'IRM multimodale encéphaliques ont été réalisés selon un protocole standard sur des appareils de 1,5 Tesla, et lus par des radiologues séniors. Nous avons confronté les résultats anatomopathologiques aux diagnostics posés à l'imagerie IRM multimodale.Résultats: Ont été retenu 18 dossiers. On notait une prédominance masculine avec un sex-ratio de 1,57. L'âge moyen était de 42,8 ans avec des extrêmes de 20ans et 61ans et un écart type de 10,75.La corrélation diagnostique entre l'examen anatomopathologique et l'IRM a été de6 sur 7 cas, 4 sur 5 cas, 2 sur 2 cas, 2 sur 2 cas et 1 sur 1 cas respectivement pour le méningiome, le gliome, les métastases, l'adénome hypophysaire, le lymphome cérébral primitif.Conclusion:Les tumeurs encéphaliques dans notre étude, étaient variéeset concernaient la population jeune. Les motifs d'erreur diagnostique étaient essentiellement en rapport avec la variété de présentations des tumeurs à l'IRM et l'expérience récente de nos radiologues sur l'utilisation efficace des séquences avancées.

Worldwide, the number of new cases of brain tumors was 14 million in 2014 with approximately 8 million people dying.Objective: determine the diagnostic effectiveness of multimodal MRI in the management of brain tumors in our context.Methods: Retrospective study with a descriptive aim, multicenter over a period of 2 years from February 2017 to March 2019, in 2 radiology departments and 2 neurosurgery departments, in Abidjan. We were interested in all patients who had a multimodal MRI for suspicion of a brain tumor process, and who had a surgical excision followed by an pathological examination of the surgical specimen. The multimodal brain MRI examinations were carried out according to a standard protocol on 1.5 Tesla devices, and read by seniorradiologists. We compared the pathological results with the diagnoses made on multimodal MRI imaging.Results:18 files were retained. There was a male predominance with a sex ratio of 1.57. The average age was 42.8 years with extremes of 20 and 61 years and a standard deviation of 10.75. The diagnostic correlation between the pathological examination and MRI was 6 out of 7 cases, 4 out of 5 cases, 2 out of 2 cases, 2 out of 2 cases and 1 out of 1 case respectively for meningioma, glioma, metastases, pituitary adenoma, primary cerebral lymphoma.Conclusion: The brain tumors in our study were varied and concerned the young population. The reasons for diagnostic error were mainly related to the variety of tumor presentations on MRI and the recent experience of our radiologists on the effective use of advanced sequences.

Research progress on brain functional near-infrared spectroscopy technology in the field of neonates / 中国当代儿科杂志

Functional near infrared spectroscopy (fNIRS) is an emerging neuroimaging tool that reflects the activity and function of brain neurons by monitoring changes in brain oxygen metabolism based on the neurovascular coupling mechanism. It is non-invasive and convenient, especially suitable for monitoring neonatal brain function. This article provides a comprehensive review of research related to the developmental patterns of brain networks concerning language, music, and emotions in neonates using fNIRS. It also covers brain network imaging in neonatal care, resting-state brain network connectivity patterns, and characteristics of brain functional imaging in disease states of neonates using fNIRS.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Research progress on mechanism of traumatic brain injury promoting fracture healing / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union.@*METHODS@#The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union.@*RESULTS@#Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity.@*CONCLUSION@#TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.

Traditional Chinese Medicine and Its Effective Components in Treating Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease is a common central neurodegenerative disease， mainly manifested by cognitive impairment and non-cognitive neuropsychiatric symptoms that severely affect patients' daily life and behavioral functioning. The pathogenesis of Alzheimer's disease is still unclear， and the western medicine currently used to treat Alzheimer's disease is only symptomatic， with a single pathway， limited efficacy， and many side effects. In recent years， with the deepening of research on Alzheimer's disease， the study and application of traditional Chinese medicine （TCM） in the treatment of Alzheimer's disease have gradually increased. Several studies have shown that TCM and its effective components can exert anti-Alzheimer's disease effects by regulating molecular mechanisms such as pathological protein production and aggregation， oxidative stress， neuroinflammation， ferroptosis， mitochondrial dysfunction， neurogenesis and neurotransmission， and brain-gut axis. This paper summarized the research progress of TCM in the treatment of Alzheimer's disease in recent years， so as to provide a reference for further study of the specific mechanism of TCM in the prevention and treatment of Alzheimer's disease and the discovery of effective components of TCM.

Biological Basis of Premature Ejaculation Based on Theory of "Brain-heart-kidney-semen Chamber" Axis / 中国实验方剂学杂志

The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine， the modern physiological characteristics of men's diseases， and clinical practice. According to this theory， dysfunctions of the brain， heart， kidney， and semen chamber are the core mechanisms for the occurrence of premature ejaculation， and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease， while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation， we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area， neuromodulation malfunction， central neurotransmitter imbalance， endocrine disorders， and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.

Research on the dynamic changes of neurological dysfunction and cognitive function impairment in traumatic brain injury / 解剖学报

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Expression and distribution of brain⁃derived neurotrophic factor in different cerebrum regions of yak and cattle / 解剖学报

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica / 解剖学报

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Recent progress of targeting Nrf2-ferroptosis to treat brain injury after ischemic stroke / 中国临床药理学与治疗学

Emerging evidences suggest that ferroptosis plays a vital role in the pathophysiological process of brain injury after Ischemic stroke. Accumulating evidence supports pharmacological inhibition of ferroptosis as a therapeutic target for brain injury after Ischemic stroke through activating nuclear factor erythroid 2-related factor 2 (Nrf2), which transcriptionally controls many key components of the ferroptosis pathway. In this review, briefly describe ferroptosis processes and the roles they play in contributing to brain injury after ischemic stroke in the brain. We then provide a critical overview of the relationship between Nrf2 signalling and ferroptosis. With a focus on discuss how therapeutic modulation of the Nrf2 pathway is a viable strategy to explore in the treatment of ferroptosis-driven brain injury after Ischemic stroke.

Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism / 中国药理学通报

Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

Application of brain organoids in environmental toxicology / 环境与职业医学

Since the 19th century, the emergence of model systems has helped researchers further understand cellular signaling pathways, identify potential drug targets, and conduct environmental toxicological studies. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect brain biological processes and functions and eventually lead to neurological diseases. However, the brain is a complex and well-organized human organ, which is fundamentally different from any existing model system. Animal models may not be able to completely simulate the human brain in testing the neurotoxicity of environmental pollutants due to species differences. Human brain organoids, generated from human pluripotent stem cells, are emerging model systems for neurotoxicological research in line with the real situation of human body at the level of genome, transcriptome, and metabolome, and provide an effective platform for testing neurotoxicity of environmental toxins. We reviewed the latest development of brain organoids technology and its application in the evaluation of environmental neurotoxins, and provided new insights into the application of brain organoids in environmental neurotoxicology.

Effect of brain-computer interface based on visual, auditory and motor feedback combined with transcranial direct current stimulation on upper limb function in stroke patients / 中国康复理论与实践

ObjectiveTo explore the effect of brain-computer interface (BCI) based on visual, auditory and motor feedback combined with transcranial direct current stimulation (tDCS) on upper limb function in stroke patients. MethodsFrom March to October, 2023, 45 stroke inpatients in Xuzhou Rehabilitation Hospital and Xuzhou Central Hospital were divided into BCI group (n = 15), tDCS group (n = 15) and combined group (n = 15) randomly. All the groups received routine rehabilitation, while BCI group received BCI training, tDCS group received tDCS, while the combined group received tDCS and followed by BCI training immediately, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT), modified Barthel Index (MBI) and delta-alpha ratio (DAR) and power ratio index (PRI) of electroencephalogram before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI increased in all the groups after treatment (|t| > 5.350, P < 0.001), and all these indexes were the best in the combined group (F > 3.366, P < 0.05); while DAR and PRI decreased in all the groups (|t| > 2.208 , P < 0.05), they were the best in the combined group (F > 5.224, P < 0.01). ConclusionBCI based on visual, auditory and motor feedback combined with tDCS can further improve the motor function of upper limbs and the activities of daily living of stroke patients.

Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability / 中国实验方剂学杂志

ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC50） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （Koff） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC50 values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller Koff values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.