title: 'Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain' description: 'The microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first-order capillaries, is the bottleneck for brain blood flow and energy supply. Exactly how aging alters the structure and function of the MIT remains unclear. By in vivo 4-dimensional two-photon imaging, we reveal an age-dependent decrease in vaso-responsivity accompanied by a decrease in vessel density close to the arterioles and loss of vascular mural cell processes, though the number of mural cell somas and their αSMA density were preserved. The age-related reduction in vascular reactivity was mostly pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed impaired pressure and flow control in aged mice during vasoconstriction. Interventions that preserve dynamics of cerebral blood vessels may ameliorate age-related decreases in blood flow and prevent brain frailty. This folder contains both the raw data and code for data analysis.All raw data related to the publications are collected in the excel file **All_Data_v2**. There are four rar code packages for data analysis. (1) **AmiraDataAnalysis.rar** Please unzip the file and load ''RawDataAnl_Vol3_Allcount3_NEW.m'' into MATLAB. This code helps analyze the Amira 3D vasculature shown in Figure 4. (2) **DiameterMeasurement.rar** Please unzip the file and load ''VesselDiameter_ByArea_GUI_MAIN.m'' into MATLAB. This code helps analyze vessel diameter change in 4D (xyzt) scanning. (3) **IHCAnalysis.rar** Please unzip the file and load ''GliaTrans_POI_GUI_MAIN.m'' into MATLAB. This code helps analyze the alpha-SMA density, pericyte and endothelial cell density from the immunohistochemical images in Figure 1. (4) **MathModel.rar** Please unzip the file and load ''amirachangsianal.py''into Python. This code makes math model of existing vasculatures to estimate the blood pressure and flow at each vessel segment.' authors: - firstname: Changsi lastname: Cai affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' id: 'ORCID: 0000-0002-7001-610X' - firstname: 'Stefan Andreas ' lastname: Zambach affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: Søren lastname: Grubb affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: Lechan lastname: Tao affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark; School of Biomedical Engineering, Shanghai Jiao-Tong University, Shanghai, China' - firstname: Chen lastname: He affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Barbara Lykke ' lastname: Lind affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Kirsten Joan ' lastname: Thomsen affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: Xiao lastname: Zhang affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Bjørn Olav ' lastname: Hald affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Reena Murmu ' lastname: Nielsen affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: Keyeon lastname: Kim affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Anna ' lastname: Devor affiliation: 'Department of Biomedical Engineering, Boston University, Boston, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA' - firstname: 'Micael ' lastname: Lønstrup affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' - firstname: 'Martin Johannes ' lastname: Lauritzen affiliation: 'Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Clinical Neurophysiology, Rigshospitalet, 2100 Copenhagen, Denmark; Center for Healthy Aging, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark' keywords: - Neuroscience - 'neurovascular coupling' - aging - 'Precapillary sphincters' - pericytes - microcirculation - capillaries - 'cerebral blood flow' license: name: 'Creative Commons CC0 1.0 Public Domain Dedication' url: 'https://creativecommons.org/publicdomain/zero/1.0/' funding: - "Lundbeck Foundation; R273-2017-1791 and R345-2020-1440\nDanish Medical Research Council; 1133-00016A\nAlice Brenaa Foundation\nAugustinus Foundation; 19-2858\nA. P. Møller Foundation; 20-L-0243\nNovo Nordisk foundation; 0064289\nNordea Foundation Grant to the Center for Healthy Aging; 02-2017-1749" references: - id: 'doi: 10.1101/2021.08.05.455300 ' reftype: IsSupplementTo citation: 'Cai, C., Zambach, S.A., Grubb, S., Thomsen, K.J., Lind, B.L., Hald, B.O., Lønstrup, M., Nielsen, R.M., Lauritzen, M.J., 2021.BioRxiv. Impaired dynamics of brain precapillary sphincters and pericytes at first order capillaries explains reduced neurovascular functions in aging' resourcetype: Dataset templateversion: 1.2