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Blood-brain barrier pathology in cerebral small vessel disease

Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3086-3109页

作者： Yihang Hao Haofan Wang Xianggen Liu Wenrui Gai Shilong Hu Wencheng Liu Zhuang Miao Yu Gan Xianghua Yu Rongjia Shi Yongzhen Tan Ting Kang Ao Hai Yi Zhao Yihang Fu Yaling Tang Ling Ye Jin Liu Xinhua Liang Bowen Ke State Key Laboratory of Oral Diseases and National Clinical Research center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China College of Computer Science Sichuan UniversityChengdu 610065China department of anesthesiology Laboratory of Anesthesia and Critical Care MedicineNational-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic *** primary challenge is to integrate diverse pharmacophores within a single-molecule *** address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local *** integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound *** framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent *** a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal *** insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome *** findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.

关键词： Multifunctional drugs Deep simulated annealing Molecule generation Articaine derivatives AI-enhanced drug discovery

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Respiratory complications of propofol,sevoflurane,and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years:a randomized trial

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南方医科大学学报 2024年第9期44卷 1631-1636页

作者： Amir Shafa Mohammad Montasery Sedighe Shahhosseini Majid Keivanfar Asieh Maghami Mehr Mahtab Ebrahim Babaei Mohammad Jafari department of anesthesiology anesthesiology and Critical Care Research center department of Pediatrics Isfahan University of Medical SciencesIsfahanIran department of Statistics Yazd UniversityYazdIran departments of Obstetrics and Gynecology Shahrekord University of Medical SciencesShahrekordIran

Objective To evaluate the effect of propofol,sevoflurane,and dexmedetomidine on respiratory complications inchildren undergoing fiberoptic bronchoscopy(FOB).Methods This double-blind randomized clinical trial was conductedamong 120 children aged 1 month to 3 years undergoing *** patients were randomized into 3 groups(n=40)foranesthesia induction with sevoflurane inhalation,1 mg/kg propofol,or 1μg/kg dexmedetomidine before bronchoscopy,andthe changes in hemodynamic parameters,sedation level,and respiratory complications during and after the procedure *** The patients'heart rate during bronchoscopy was significantly lower and the mean arterial blood pressuresignificantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P2.5%)was significantly lower than those insevoflurane and dexmedetomidine groups(30%and 32.5%,respectively)(P<0.05).Conclusion Sevoflurane and propofol aresafe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve bettersedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

关键词： fiberoptic bronchoscopy propofol sevoflurane dexmedetomidine children

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Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

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Neural Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Golam Jiamei Hou Kevin K.W.Wang Floyd J.Thompson Prodip Bose Brain Rehabilitation Research center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA department of anesthesiology College of MedicineUniversity of FloridaGainesvilleFLUSA department of Emergency Medicine University of FloridaGainesvilleFLUSA department of neuroscience University of FloridaGainesvilleFLUSA department of Neurology University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain *** has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb ***,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in *** three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid *** results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham *** other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically *** results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular *** is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

关键词： balance blood flow cardiovascular system central nervous system epinephrine ischemic damage lumbar spinal cord muscle tone repeated blast spasticity traumatic brain injury

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Respiratory complications of propofol, sevoflurane, and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years: a randomized trial

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南方医科大学学报 2024年

作者： Amir Shafa Mohammad Montasery Sedighe Shahhosseini Majid Keivanfar Asieh Maghami Mehr Mahtab Ebrahim Babaei Mohammad Jafari department of anesthesiology anesthesiology and Critical Care Research center department of Pediatrics Isfahan University of Medical Sciences department of Statistics Yazd University departments of Obstetrics and Gynecology Shahrekord University of Medical Sciences

Objective To evaluate the effect of propofol, sevoflurane, and dexmedetomidine on respiratory complications in children undergoing fiberoptic bronchoscopy(FOB). Methods This double-blind randomized clinical trial was conducted among 120 children aged 1 month to 3 years undergoing FOB. The patients were randomized into 3 groups(n=40) for anesthesia induction with sevoflurane inhalation, 1 mg/kg propofol, or 1 μg/kg dexmedetomidine before bronchoscopy, and the changes in hemodynamic parameters, sedation level, and respiratory complications during and after the procedure were assessed. Results The patients' heart rate during bronchoscopy was significantly lower and the mean arterial blood pressure significantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P2.5%) was significantly lower than those in sevoflurane and dexmedetomidine groups(30% and 32.5%, respectively)(P<0.05). Conclusion Sevoflurane and propofol are safe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve better sedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

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Dynamic Organization of Large-scale Functional Brain Networks Supports Interactions Between Emotion and Executive Control

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neuroscience Bulletin 2024年第7期40卷 981-991页

作者： Haiyang Geng Pengfei Xu Andre Aleman Shaozheng Qin Yue-Jia Luo State Key Laboratory of Cognitive neuroscience and Learning Beijing Normal UniversityBeijing 100875China Tianqiao and Chrissy Chen Institute for Translational ResearchShanghai 200040China Beijing Key Laboratory of Applied Experimental Psychology National Demonstration Center for Experimental Psychology Education(BNU)Faculty of PsychologyBeijing Normal UniversityBeijing 100875China center for Neuroimaging Shenzhen Institute of NeuroscienceShenzhen 518107China University of Groningen Department of Biomedical Sciences of Cells and SystemsSection Cognitive NeuroscienceUniversity Medical Center GroningenGroningenThe Netherlands Institute for Neuropsychological Rehabilitation University of Health and Rehabilitation SciencesQingdao 266113China Shenzhen Key Laboratory of Affective and Social neuroscience Magnetic Resonance ImagingCenter for Brain Disorders and Cognitive SciencesShenzhen UniversityShenzhen 518060China Chinese Institute for Brain Research Beijing 102206China

Emotion and executive control are often conceptualized as two distinct modes of human brain ***,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their *** amygdala and prefrontal systems have long been thought to play crucial roles in these *** advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their ***,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based *** this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain *** model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.

关键词： Dynamic brain network Emotion Executive control Salience network Executive control network Default mode network

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New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

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Neural Regeneration Research 2024年第9期19卷 1867-1868页

作者： MacKenzie A.Howard department of Neurology Dell Medical SchoolAustinTXUSA center for Learning and Memory and department of neuroscience University of Texas at AustinAustinTXUSA

Developmental and epileptic encephalopathies(DEEs)are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition,mood,sleep,social behavior,movement control,learning,and/or *** syndrome(DS),also known as Severe Myoclonic Epilepsy of Infancy.

关键词： sized finding seizures

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Ultrasound-guided sphenopalatine ganglion block for effective analgesia during awake fiberoptic nasotracheal intubation: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2451-2456页

作者： Hangil Kang Seongjae Park Yehun Jin department of anesthesiology and Pain Medicine National Cancer CenterGoyang-si 10408Gyeonggi-doSouth Korea

BACKGROUND Awake fiberoptic nasotracheal intubation(AFNI)is the preferred airway ma-nagement strategy for patients with difficult ***,this procedure can cause significant physical and psychological *** case report explores the application of a sphenopalatine ganglion(SPG)block as an alternative anal-gesic modality to mitigate the discomfort associated with *** SUMMARY A 63-year-old female with a history of right maxillary osteosarcoma underwent craniotomy for a suspected malignant brain *** patient’s medical history included prior surgery,chemotherapy,and radiation therapy,resulting in signi-ficant jaw impairment and limited neck *** the anticipated air-way challenges,AFNI was planned.A SPG block was performed under real-time ultrasound guidance,providing effective analgesia during nasotracheal *** The SPG block represents a promising analgesic approach in AFNI,offering po-tential benefits in alleviating pain involving the nasal and nasopharyngeal regions as well as improving patient cooperation.

关键词： Sphenopalatine ganglion block Nerve block Regional anesthesia Analgesia Awake fiberoptic nasotracheal intubation Case report

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Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

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Neural Regeneration Research 2024年第3期19卷 493-494页

作者： Melissa Schepers Tim Vanmierlo department of neuroscience Biomedical Research InstituteFaculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium department of Psychiatry and Neuropsychology School for Mental Health and NeuroscienceMaastricht UniversityMaastrichtNetherlands University MS center(UMSC)Hasselt-Pelt HasseltBelgium

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is ***,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon *** to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in ***,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

关键词： impaired inflammation Marie

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