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Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2306-2325页

作者： Liang Han Chen Jiang Jiangsu Key Laboratory of Neuropsychiatric diseases Research College of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China Key Laboratory of Smart Drug Delivery Ministry of EducationState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 200032China

Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain ***,during the onset and progression of brain diseases,BBB alterations evolve *** this review,we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer’s disease,Parkinson’s disease,epilepsy,stroke,traumatic brain injury and brain *** advances on optimization of small molecules for BBB crossing and non-systemic administration routes(e.g.,intranasal treatment)for BBB bypassing are not included in this review.

关键词： Blood-brain barrier brain diseases brain-targeting Drug delivery systems Nanoparticles

Using induced pluripotent stem cells derived neurons to model brain diseases

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Neural Regeneration Research 2017年第7期12卷 1062-1067页

作者： Cindy E.McKinney iPSC Lab/Edward Via College of Osteopathic Medicine and The Gibbs Research Institute Spartanburg SC USA

The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these *** models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human *** derived neurons,or other neural cell types,provide the ability to access pathology in cells derived directly from a patient＇s blood sample or skin biopsy where availability of brain tissue is ***,utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the *** brain diseases across the spectrum of neurodevelopment,neurodegenerative and neuropsychiatric are being approached by iPSC *** goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control *** this mini-review,the importance of iPSC cell models validated for pluripotency,germline competency and function assessments is *** examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

关键词： induced pluripotent stem cells neuron cell models brain diseases molecular mechanisms therapeutics translational medicine

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静电纺纤维滴鼻液实现脑室内给药

Science Bulletin 2024年第9期69卷 1249-1262页

作者：王娟王秋云符一飞卢敏陈亮刘志恒付晓晗杜习羽于布为陆菡崔文国 Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Anesthesiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Anesthesiology Shenzhen Second People’s HospitalThe First Afﬁliated Hospital of Shenzhen UniversityShenzhen 518035China Department of Anesthesiology Huadong Hospital Afﬁliated to Fudan UniversityShanghai 200040China

Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

关键词： Nasal drops Electrospun short fibers Nasal mucosa Intraventricular administration brain diseases

Feature Enhanced Stacked Auto Encoder for diseases Detection in brain MRI

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Computers, Materials & Continua 2023年第8期76卷 2551-2570页

作者： Umair Muneer Butt Rimsha Arif Sukumar Letchmunan Babur Hayat Malik Muhammad Adil Butt School of Computer Sciences Universiti Sains MalaysiaPenang1180Malaysia Department of Computer Science and IT The University of ChenabGujrat50700Pakistan

The detection of brain disease is an essential issue in medical and research *** learning techniques have shown promising results in detecting and diagnosing brain diseases using magnetic resonance imaging(MRI)*** techniques involve training neural networks on large datasets of MRI images,allowing the networks to learn patterns and features indicative of different brain ***,several challenges and limitations still need to be addressed further to improve the accuracy and effectiveness of these *** paper implements a Feature Enhanced Stacked Auto Encoder(FESAE)model to detect brain *** standard stack auto encoder’s results are trivial and not robust enough to boost the system’s ***,the standard Stack Auto Encoder(SAE)is replaced with a Stacked Feature Enhanced Auto Encoder with a feature enhancement function to efficiently and effectively get non-trivial features with less activation energy froman *** proposed model consists of four ***,pre-processing is performed to remove noise,and the greyscale image is converted to Red,Green,and Blue(RGB)to enhance feature details for discriminative feature ***,feature Extraction is performed to extract significant features for classification using DiscreteWavelet Transform(DWT)and ***,classification is performed to classify MRI images into four major classes:Normal,Tumor,brain Stroke,and Alzheimer’***,the FESAE model outperforms the state-of-theart,machine learning,and deep learning methods such as Artificial Neural Network(ANN),SAE,Random Forest(RF),and Logistic Regression(LR)by achieving a high accuracy of 98.61% on a dataset of 2000 MRI *** proposed model has significant potential for assisting radiologists in diagnosing brain diseases more accurately and improving patient outcomes.

关键词： brain diseases deep learning feature enhanced stacked auto encoder stack auto encoder

Advances in electrical impedance tomography-based brain imaging

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Military Medical Research 2022年第6期9卷 705-726页

作者： Xi-Yang Ke Wei Hou Qi Huang Xue Hou Xue-Ying Bao Wei-Xuan Kong Cheng-Xiang Li Yu-Qi Qiu Si-Yi Hu Li-Hua Dong Department of Radiation Oncology and Therapy the First Hospital of Jilin UniversityChangchun 130021China Jilin Provincial Key Laboratory of Radiation Oncology and Therapy the First Hospital of Jilin UniversityChangchun 130021China NHC Key Laboratory of Radiobiology School of Public HealthJilin UniversityChangchun 130021China CAS Key Laboratory of Bio-Medical Diagnostics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhou 215163JiangsuChina

Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography(EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies,which has led to its potential clinical use. This qualitative review provides an overview of the basic principles,algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy,stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth,from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry,inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.

关键词： Electrical impedance tomography(EIT) brain diseases Tissue impedance Microelectrode array

Nanotechnologies meeting natural sources:Engineered lipoproteins for precise brain disease theranostics

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Asian Journal of Pharmaceutical Sciences 2023年第5期18卷 77-98页

作者： Ruoning Wang Xinru Zhang Kuanhan Feng Wei Zeng Jie Wu Danni Sun Ziyi Lu Hao Feng Liuqing Di School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System Nanjing 210023China

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic ***,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain ***,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical *** address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical *** this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are ***,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are ***,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively ***,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.

关键词： Biological modulation brain diseases Blood-brain barrier Lipoproteins Theranostics

Reading impairment after neonatal hypoglycemia with parietotemporo-occipital injury without cortical blindness:A case report

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World Journal of Clinical Cases 2023年第16期11卷 3899-3906页

作者： Naoko Kurahashi Shunsuke Ogaya Yuki Maki Norie Nonobe Sumire Kumai Yosuke Hosokawa Chikako Ogawa Keitaro Yamada Koichi Maruyama Kiyokuni Miura Miho Nakamura Department of Pediatric Neurology Central HospitalAichi Developmental Disability CenterKasugai 480-0392AichiJapan Department of Pediatrics Nagoya University Graduate School of MedicineNagoya 466-8560AichiJapan Division of Neonatology Center for Maternal-Neonatal Care Nagoya University HospitalNagoya 466-8560AichiJapan Department of Pediatrics Tokyo Metropolitan Fuchu Medical Center for the DisabledFuchu 183-0042TokyoJapan Department of Functioning and Disability Institute for Developmental ResearchAichi Developmental Disability CenterKasugai 480-0392AichiJapan Okazaki Medical Center for Child Development Okazaki 444-0011AichiJapan

BACKGROUND Perinatal brain injury may lead to later neurodevelopmental disorders,whose outcomes may vary due to neuroplasticity in young *** neuroimaging studies have shown that the left parietotemporal area(which includes the left inferior parietal lobe)is associated with phonological awareness and decoding skills,which are essential skills for reading acquisition in ***,the literature on the effect of perinatal cerebral injury on the development of phonological awareness or decoding ability in childhood is *** SUMMARY We report the case of an 8-year-old boy who presented with reading difficulty following a perinatal injury in the parieto-temporal-occipital *** patient was born at term and was treated for hypoglycemia and seizures during the neonatal ***-weighted brain magnetic resonance imaging on postnatal day 4 revealed cortical and subcortical hyperintensities in the parieto-temporo-occipital *** the age of 8 years,physical examination was unremarkable,aside from mild *** occipital lobe injury,the patient had adequate visual acuity,normal eye movement,and no visual field ***-scale intelligence quotient and verbal comprehension index on Wechsler Intelligence Scale for Children-Fourth Edition were 75 and 90,*** assessment revealed adequate recognition of Japanese Hiragana ***,he had significantly slower reading speed in the Hiragana reading test than control *** phonological awareness test revealed significant errors(standard deviation+2.7)in the mora reversal *** Patients with perinatal brain injuries in the parietotemporal area require attention and may benefit from additional reading instructions.

关键词： brain diseases Hypoglycemia Dyslexia Long-term care Education Case report

Measurement of Cerebral Oxygen Extraction Fraction Using Quantitative BOLD Approach:A Review

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Phenomics 2023年第1期3卷 101-118页

作者： Hongwei Li Chengyan Wang Xuchen Yu Yu Luo He Wang Institute of Science and Technology for brain-Inspired Intelligence Fudan University220 Handan RoadYangpu DistrictShanghai 200433China Human Phenome Institute Fudan UniversityShanghai 201203China Department of Radiology Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Key Laboratory of Computational Neuroscience and brain-Inspired Intelligence (Fudan University)Ministry of EducationShanghai 200433China

Quantification of brain oxygenation and metabolism,both of which are indicators of the level of brain activity,plays a vital role in understanding the cerebral perfusion and the pathophysiology of brain *** resonance imaging(MRI),a widely used clinical imaging technique,which is very sensitive to magnetic susceptibility,has the possibility of substitut-ing positron emission tomography(PET)in measuring oxygen *** review mainly focuses on the quantitative blood oxygenation level-dependent(qBOLD)method for the evaluation of oxygen extraction fraction(OEF)in the ***,we review the theoretic basis of qBOLD,as well as existing acquisition and quantification *** published clinical studies are also presented,and the pros and cons of qBOLD method are discussed as well.

关键词： Quantitative BOLD Oxygen extraction fraction Static dephasing regime brain diseases

Deciphering brain Complexity Using Single-cell Sequencing

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 344-366页

作者： Quanhua Mu Yiyun Chen Jiguang Wang Department of Chemical and Biological Engineering Division of Life Science Center for Systems Biology and Human Health and State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology

The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions,such as memory,decision-making,and social *** data is required to decipher the complexity of cell types,as well as connectivity and functions of the *** newly developed single-cell sequencing technology,which provides a comprehensive landscape of brain cell type diversity by profiling the transcriptome,genome,and/or epigenome of individual cells,has contributed substantially to revealing the complexity and dynamics of the brain and providing new insights into brain development and brain-related *** this review,we first introduce the progresses in both experimental and computational methods of single-cell sequencing *** of single-cell sequencing-based technologies in brain research,including cell type classification,brain development,and brain disease mechanisms,are then elucidated by representative ***,we provided our perspectives into the challenges and future developments in the field of single-cell *** summary,this mini review aims to provide an overview of how big data generated from single-cell sequencing have empowered the advancements in neuroscience and shed light on the complex problems in understanding brain functions and diseases.

关键词： Neuroscience Single-cell RNA-seq Cell type brain development brain diseases