Dataset
Impaired dynamics of precapillary sphincters and pericytes at first-order capillaries predict reduced neurovascular function in the aging mouse brain
- 1Department of Neuroscience, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark
- 2School of Biomedical Engineering, Shanghai Jiao-Tong University, Shanghai, China
- 3Department of Biomedical Engineering, Boston University, Boston, USA
- 4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA
- 5Department of Clinical Neurophysiology, Rigshospitalet, 2100 Copenhagen, Denmark
- 6Center for Healthy Aging, Faculty of Health and Medical Science, University of Copenhagen, 2200 Copenhagen, Denmark
DOI: 10.12751/g-node.zcg4cy BROWSE REPOSITORY BROWSE ARCHIVE DOWNLOAD ARCHIVE (ZIP 8.4 MiB)
Published 29 Nov. 2022 | License Creative Commons CC0 1.0 Public Domain Dedication
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.
Keywords
| Neuroscience | neurovascular coupling | aging | Precapillary sphincters | pericytes | microcirculation | capillaries | cerebral blood flow |References
- 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) Impaired dynamics of brain precapillary sphincters and pericytes at first order capillaries explains reduced neurovascular functions in aging. BioRxiv 2021.08.05.455300. https://doi.org/10.1101/2021.08.05.455300
Funding
- Lundbeck Foundation R273-2017-1791 and R345-2020-1440
- Danish Medical Research Council 1133-00016A
- Alice Brenaa Foundation, Augustinus Foundation 19-2858
- A. P. Møller Foundation 20-L-0243
- Novo Nordisk foundation 0064289
- Nordea Foundation Grant to the Center for Healthy Aging 02-2017-1749