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      Pathological changes in neurovascular units: Lessons from cases of vascular dementia

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          Abstract

          Vascular dementia (VD) is the second leading cause of dementia after Alzheimer's disease (AD). The decrease of cerebral blood flow (CBF) to different degrees is one of the main causes of VD. Neurovascular unit (NVU) is a vessel‐centered concept, emphasizing all the cellular components play an integrated role in maintaining the normal physiological functions of the brain. More and more evidence shows that reduced CBF causes a series of changes in NVU, such as impaired neuronal function, abnormal activation of glial cells, and changes in vascular permeability, all of which collectively play a role in the pathogenesis of VD. In this paper, we review NVU changes as CBF decreases, focusing on each cellular component of NVU. We also highlight remote ischemic preconditioning as a promising approach for VD prevention and treatment from the NVU perspective of view.

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          Most cited references127

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          Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

          Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
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            An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.

            The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain. Copyright © 2014 the authors 0270-6474/14/3411929-19$15.00/0.
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              Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.

              The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.
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                Author and article information

                Contributors
                zhen1ni2@jlu.edu.cn , zhen1ni2@163.com
                yang_yi@jlu.edu.cn , doctoryangyi@163.com
                Journal
                CNS Neurosci Ther
                CNS Neurosci Ther
                10.1111/(ISSN)1755-5949
                CNS
                CNS Neuroscience & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                1755-5930
                1755-5949
                10 January 2021
                January 2021
                : 27
                : 1 , Neurovascular Unit Protection ( doiID: 10.1111/cns.v27.1 )
                : 17-25
                Affiliations
                [ 1 ] Department of Neurology Stroke Center & Clinical Trial and Research Center for Stroke the First Hospital of Jilin University Changchun China
                [ 2 ] China National Comprehensive Stroke Center Changchun China
                [ 3 ] Jilin Provincial Key Laboratory of Cerebrovascular Disease Changchun China
                Author notes
                [*] [* ] Correspondence

                Zhen‐Ni Guo and Yi Yang, Stroke Center & Clinical Trial and Research Center for Stroke, Department of Neurology, the First Hospital of Jilin University, No.1 Xinmin Street, Changchun 130021, China.

                Email: zhen1ni2@ 123456jlu.edu.cn ; zhen1ni2@ 123456163.com (Z. ‐N. G.) and yang_yi@ 123456jlu.edu.cn ; doctoryangyi@ 123456163.com (Y. Y.)

                Author information
                https://orcid.org/0000-0001-6332-5935
                Article
                CNS13572
                10.1111/cns.13572
                7804924
                33423390
                c025e333-31f8-4614-8743-f67cfbcc851c
                © 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 August 2020
                : 13 December 2020
                : 14 December 2020
                Page count
                Figures: 1, Tables: 0, Pages: 9, Words: 7803
                Funding
                Funded by: JLUSTIRT
                Award ID: 2017TD‐12
                Funded by: National Natural Science Foundation of China
                Award ID: 81771243
                Funded by: Jilin Provincial Key Laboratory
                Award ID: 20190901005JC
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:21.01.2021

                Neurosciences
                cerebral blood flow,neurovascular units,remote ischemic conditioning,vascular dementia

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