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The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured neurovascular unit

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Biomedical and Environmental Sciences 2024年第7期37卷 726-738页

作者： Fang Xue Wenchao Chen Xia Lian Guanghui He Jingyuan Tian Yinghong Liu Gaiqing Wang Department of Neurology The Second Clinical School of MedicineShanxi Medical UniversityTaiyuan 030002ShanxiChina The Second Clinical School of Medicine Shanxi Medical UniversityTaiyuan 030002ShanxiChina Department of Clinical lab The First People’s Hospital of ZhaotongZhaotong 657000YunnanChina Department of Neurology Sanya Central Hospital(Hainan Third People’s Hospital)Hainan Medical UniversitySanya 57200HainanChina

disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic *** clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after *** study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance *** The transwell model and hemoglobin were co-cultured to simulate the BBB environment after *** intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively *** Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial ***,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU’s endogenous brain clearance *** Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

关键词： Blood-brain barrier Circadian rhythm neurovascular unit Melatonin receptor 1A Aquaporin-4

Efficacy of Sailuotong(塞络通)on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer's disease

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Journal of Traditional Chinese Medicine 2024年第2期44卷 289-302页

作者： SUN Linjuan LI Chengfu LIU Jiangang LI Nannan HAN Fuhua QIAO Dandan TAO Zhuang ZHAN Min CHEN Wenjie ZHANG Xiaohui TONG Chenguang CHEN Dong Qi Jiangxia LIU Yang LIANG Xiao ZHENG Xiaoying ZHANG Yunling Department of Neurology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China China Population and Development Research Center Beijing 100081China Department of Institute of Population Research Peking UniversityBeijing 100087China Graduate School of China Academy of Chinese Medical Sciences Beijing 100700China Graduate School of Beijing University of Chinese Medicine Beijing 100029China

OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the neurovascular unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a *** Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of *** hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red *** ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western *** mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by *** results of HE staining showed that SLT restored the pathological changes of the *** Congo red staining results revealed that SLT also improved the scattered

关键词： Alzheimer disease amyloid beta-protein precursor presenilin-1 mice transgenic replenishing Qi and activating blood neurovascular unit Sailuotong

A neurovascular unit-on-a-chip:culture and differentiation of human neural stem cells in a three-dimensional microfluidic environment

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Neural Regeneration Research 2022年第10期17卷 2260-2266页

作者： Wen-Juan Wei Ya-Chen Wang Xin Guan Wei-Gong Chen Jing Liu Stem Cell Clinical Research Center National Joint Engineering LaboratoryRegenerative Medicine Centerthe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina

Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external *** technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high *** combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular *** model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe *** provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the *** in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.

关键词： (neural)differentiation astrocyte blood-brain barrier brain microvascular endothelial cells central nervous system microfluidics neural stem cells neuron neurovascular unit oligodendrocyte organ-on-a-chip

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2023年第4期18卷 869-874页

作者： Xiao-Yu Zhu Ting-Ting Ma Yang Li Ming-Qi Zhang Liang Zhao Jia Liang Lian-Qiu Min Department of Neurology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina Institution of Life Science Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina School of Pharmacy Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein ***(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular *** the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia *** results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic *** protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein *** findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

关键词： astrocyte blood-brain barrier claudin-5 FTY-720 interleukin-17A ischemic stroke neural protection neurovascular unit occludin sphingosine-1-phosphate receptor 1

Construction and imaging of a neurovascular unit model

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Neural Regeneration Research 2022年第8期17卷 1685-1694页

作者： Taiwei Dong Min Li Feng Gao Peifeng Wei Jian Wang College of Pharmacy Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina College of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinveChina

In 2001,the concept of the neurovascular unit was introduced at the Stroke Progress Review Group *** neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous *** then,the neurovascular unit has attracted increasing interest from research teams,who have contributed greatly to the prevention,treatment,and prognosis of stroke and neurodegenerative ***,additional research is needed to establish an efficient,low-cost,and low-energy in vitro model of the neurovascular unit,as well as enable noninvasive observation of neurovascular units in vivo and in *** this review,we first summarize the composition of neurovascular units,then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models,and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.

关键词： 3D printing blood-brain barrier computational biology encephalopathy imaging techniques microfluidic on-chip methods nerve cell co-culture neurovascular unit review stem cells

Dysfunction of the neurovascular unit in brain aging

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The Journal of Biomedical Research 2023年第3期37卷 153-165页

作者： Shu Liu Xu Yang Fei Chen Zhiyou Cai Chongqing Medical University Chongqing 400042China Chongqing Institute Green and Intelligent Technology Chinese Academy of SciencesChongqing 400714China Chongqing School University of Chinese Academy of SciencesChongqing 400714China Department of Neurology Chongqing General HospitalChongqing 400013China Chongqing Key Laboratory of Neurodegenerative Diseases Chongqing 400013China.

An emerging concept termed the neurovascular unit(NVU)underlines neurovascular *** has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson's *** is a complex and irreversible process caused by programmed and damage-related *** of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of *** this review,we describe the basics of the NVU and discuss the effect of aging on NVU ***,we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases,such as Alzheimer's disease and Parkinson's ***,we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.

关键词： aging neurovascular unit Alzheimer's disease Parkinson's disease

neurovascular unit in diabetic retinopathy:pathophysiological roles and potential therapeutical targets

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Eye and Vision 2021年第3期8卷 135-153页

作者： Shen Nian Amy C.Y.Lo Yajing Mi Kai Ren Di Yang Department of Pathology Xi’an Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology LKS Faculty of MedicineThe University of Hong KongHong KongHong Kong Institute of Basic Medicine Science Xi’an Medical UniversityXi’anShaanxi ProvinceChina Department of Biochemistry and Molecular Biology Xi’an Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology First Affiliated Hospital of Kunming Medical UniversityKunming Medical UniversityKunmingYunnan ProvinceChina

Diabetic retinopathy(DR),one of the common complications of diabetes,is the leading cause of visual loss in working-age individuals in many industrialized *** has been traditionally regarded as a purely microvascular disease in the ***,an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the *** of neural retina could precede microvascular abnormalities in the DR,leading to microvascular ***,disruption of interactions among neurons,vascular cells,glia and local immune cells,which collectively form the neurovascular unit,is considered to be associated with the progression of DR early on in the ***,it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration,neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage ***,we present current perspectives on the pathophysiology of DR as a neurovascular disease,especially at the early *** novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.

关键词： Diabetic retinopathy neurovascular unit Neurodegeneration Gliosis Inflammation treatment

Effects of Ferulic Acid on Regulating the neurovascular unit:Implications for Ischemic Stroke Treatment

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World Journal of Traditional Chinese Medicine 2022年第2期8卷 210-217页

作者： Xiang Wang Xin-Ran Liu Ke-Xin Li Xiang Fan Yang Liu Graduate School Tianjin University of Traditional Chinese MedicineTianjinChina School of Chinese Materia Medic Tianjin University of Traditional Chinese MedicineTianjinChina Zhejiang Chinese Medical University ZhejiangChina Chinese Medical College Tianjin University of Traditional Chinese MedicineTianjinChina

Ferulic acid(FA)is a phenolic phytochemical with antioxidant and anti-inflammatory pharmacological *** recent years,the neuroprotective effects of FA have been studied *** researchers have attempted to use FA to prevent and treat neurological diseases and have made some *** paper mainly collated the study of the protective effect of FA on stroke and summarized the protective effect of FA on ischemic stroke and the potential protective effects of FA on neurovascular units.

关键词： Ferulic acid ischemic stroke neuroprotective effects neurovascular unit

Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

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Neural Regeneration Research 2021年第11期16卷 2132-2140页

作者： Tara M.Caffrey Emily B.Button Jerome Robert Djavad Mowafaghian Center for Brain Health University of British ColumbiaVancouverBCCanada Department of Pathology University of British ColumbiaVancouverBCCanada Institute of Clinical Chemistry University Hospital of ZurichZurichSwitzerland

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and *** supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular *** many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the *** order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular *** towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous *** and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the *** advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential *** innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

关键词： Alzheimer’s disease cerebrovasculature in vitro model neurodegeneration neurovascular unit