The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes
Open accessAbstract
Summary The precise regulation of cerebral blood flow is critical for normal brain function and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar smooth muscle cells.
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1 retracted
RETRACTED ARTICLE: Pericyte loss influences Alzheimer-like neurodegeneration in mice
Sagare, A. P., Bell, R. D., Zhao, Z., Ma, Q., Winkler, E. A., Ramanathan, A., & Zlokovic, B. V. (2013) · Nature Communications · doi:10.1038/ncomms3932 · Cited by 589
RetractedNeurophysiological investigation of the basis of the fMRI signal
Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A. (2001) · Nature · doi:10.1038/35084005 · Cited by 6,551
Brain magnetic resonance imaging with contrast dependent on blood oxygenation.
Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.24.9868 · Cited by 6,483
Pericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843
Neurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213
Pericytes are required for blood–brain barrier integrity during embryogenesis
Daneman, R., Zhou, L., Kebede, A. A., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09513 · Cited by 2,128
Capillary pericytes regulate cerebral blood flow in health and disease
Hall, C. N., Reynell, C., Gesslein, B., Hamilton, N. B., Mishra, A., Sutherland, B. A., O’Farrell, F. M., Buchan, A. M., Lauritzen, M., & Attwell, D. (2014) · Nature · doi:10.1038/nature13165 · Cited by 1,870
Kety, S. S., & Schmidt, C. F. (1948) · Journal of Clinical Investigation · doi:10.1172/jci101995 · Cited by 1,827 · cited 2×
“…the mechanisms controlling neurovascular coupling are not well understood, previous work demonstrates the involvement of complex interactions between neurons, glia, and vascular cells (Haydon and Carmignoto, 2006; Iadecola and Nedergaard, 2007; Kety and Schmidt, 1948; Roy and Sherrington , 1890).”
Raichle, M. E., & Mintun, M. A. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112819 · Cited by 1,630
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448
Cited by
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480
A molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 1,892
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
“Mural cells have two subtypes: pericytes, which associate with capillaries, and smooth muscle alpha actin (SMA) cells, which associate with larger-bore vasculature and control blood flow (Hill et al., 2015; Hughes and Chan-Ling, 2004; Nehls and Drenckhahn, 1991).”
BackgroundCerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease
Kisler, K., Nelson, A. R., Montagne, A., & Zlokovic, B. V. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.48 · Cited by 1,243
Pericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125
The role of brain vasculature in neurodegenerative disorders
Sweeney, M. D., Kisler, K., Montagne, A., Toga, A. W., & Zlokovic, B. V. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0234-x · Cited by 998
Vascular heterogeneity and specialization in development and disease
Potente, M., & Mäkinen, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.36 · Cited by 653
Attwell, D., Mishra, A., Hall, C. N., O’Farrell, F. M., & Dalkara, T. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15610340 · Cited by 648
Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease
Nelson, A. R., Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.016 · Cited by 559
Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain
Kisler, K., Nelson, A. R., Rege, S. V., Ramanathan, A., Wang, Y., Ahuja, A., Lazic, D., Tsai, P. S., Zhao, Z., Zhou, Y., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4489 · Cited by 497
Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain
Hill, R. A., Li, A. M., & Grutzendler, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0120-6 · Cited by 467
Self-citationPericytes and Neurovascular Function in the Healthy and Diseased Brain
Brown, L. S., Foster, C. G., Courtney, J.-M., King, N. E., Howells, D. W., & Sutherland, B. A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00282 · Cited by 406
Faraco, G., Sugiyama, Y., Lane, D., Garcia-Bonilla, L., Chang, H., Santisteban, M. M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86950 · Cited by 350
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348
The capillary bed offers the largest hemodynamic resistance to the cortical blood supply
Gould, I. G., Tsai, P., Kleinfeld, D., & Linninger, A. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16671146 · Cited by 252
Brain and Retinal Pericytes: Origin, Function and Role
Trost, A., Lange, S., Schroedl, F., Bruckner, D., Motloch, K. A., Bogner, B., Kaser-Eichberger, A., Strohmaier, C., Runge, C., Aigner, L., et al. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00020 · Cited by 244
Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain
Berthiaume, A.-A., Grant, R. I., McDowell, K. P., Underly, R. G., Hartmann, D. A., Levy, M., Bhat, N. R., & Shih, A. Y. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.016 · Cited by 223
Analysis of the brain mural cell transcriptome
He, L., Vanlandewijck, M., Raschperger, E., Andaloussi Mäe, M., Jung, B., Lebouvier, T., Ando, K., Hofmann, J., Keller, A., & Betsholtz, C. (2016) · Scientific Reports · doi:10.1038/srep35108 · Cited by 233
Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control
Haddad-Tóvolli, R., Dragano, N. R. V., Ramalho, A. F. S., & Velloso, L. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00224 · Cited by 226
Human pluripotent stem cell–derived brain pericyte–like cells induce blood-brain barrier properties
Stebbins, M. J., Gastfriend, B. D., Canfield, S. G., Lee, M.-S., Richards, D., Faubion, M. G., Li, W.-J., Daneman, R., Palecek, S. P., & Shusta, E. V. (2019) · Science Advances · doi:10.1126/sciadv.aau7375 · Cited by 195
Neurovascular Dysfunction in Vascular Dementia, Alzheimer's and Atherosclerosis
Shabir, O., Berwick, J., & Francis, S. E. (2018) · BMC Neuroscience · doi:10.1186/s12868-018-0465-5 · Cited by 191
Zimmerman, B., Rypma, B., Gratton, G., & Fabiani, M. (2021) · Psychophysiology · doi:10.1111/psyp.13796 · Cited by 179
Exploring early human brain development with structural and physiological neuroimaging
Vasung, L., Abaci Turk, E., Ferradal, S. L., Sutin, J., Stout, J. N., Ahtam, B., Lin, P.-Y., & Grant, P. E. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2018.07.041 · Cited by 177
Pericytes impair capillary blood flow and motor function after chronic spinal cord injury
Li, Y., Lucas-Osma, A. M., Black, S., Bandet, M. V., Stephens, M. J., Vavrek, R., Sanelli, L., Fenrich, K. K., Di Narzo, A. F., Dracheva, S., et al. (2017) · Nature Medicine · doi:10.1038/nm.4331 · Cited by 164
Benchmarking in vitro tissue-engineered blood–brain barrier models
DeStefano, J. G., Jamieson, J. J., Linville, R. M., & Searson, P. C. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0117-2 · Cited by 142
Glial Cell Calcium Signaling Mediates Capillary Regulation of Blood Flow in the Retina
Biesecker, K. R., Srienc, A. I., Shimoda, A. M., Agarwal, A., Bergles, D. E., Kofuji, P., & Newman, E. A. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1782-16.2016 · Cited by 144
Jamieson, J. J., Linville, R. M., Ding, Y. Y., Gerecht, S., & Searson, P. C. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0136-7 · Cited by 117
Dysfunction of brain pericytes in chronic neuroinflammation
Persidsky, Y., Hill, J., Zhang, M., Dykstra, H., Winfield, M., Reichenbach, N. L., Potula, R., Mukherjee, A., Ramirez, S. H., & Rom, S. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15606149 · Cited by 116
Grifno, G. N., Farrell, A. M., Linville, R. M., Arevalo, D., Kim, J. H., Gu, L., & Searson, P. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-50193-1 · Cited by 112
The role of the blood–brain barrier during neurological disease and infection
Patabendige, A., & Janigro, D. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220830 · Cited by 112
Interplay between Brain Pericytes and Endothelial Cells in Dementia
Procter, T. V., Williams, A., & Montagne, A. (2021) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.07.003 · Cited by 106
(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.02.006 · Cited by 87
Nelson, A. R., Sagare, M. A., Wang, Y., Kisler, K., Zhao, Z., & Zlokovic, B. V. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00108 · Cited by 73
Cudmore, R. H., Dougherty, S. E., & Linden, D. J. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16682508 · Cited by 54
Second Near‐Infrared Window Fluorescence Materials for In Vivo Dynamic Multiplexed Imaging
Fan, F., Zeng, K., Zhu, Y., Zhang, Y., Chen, Y., Lv, D., Jia, D., Chai, Y., Chen, X., & Li, Q. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202422693 · Cited by 33
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction
Hansen, C. E., Vacondio, D., van der Molen, L., Jüttner, A. A., Fung, W. K., Karsten, M., van het Hof, B., Fontijn, R. D., Kooij, G., Witte, M. E., et al. (2025) · Cell Death & Disease · doi:10.1038/s41419-024-07306-0 · Cited by 27
Steinman, J., Cahill, L. S., Koletar, M. M., Stefanovic, B., & Sled, J. G. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116101 · Cited by 24
Kozberg, M. G., Munting, L. P., Hanlin, L. H., Auger, C. A., van den Berg, M. L., Denis de Senneville, B., Hirschler, L., Warnking, J. M., Barbier, E. L., Farrar, C. T., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf186 · Cited by 23
Ji, Y., Chen, Y., Tan, X., Huang, X., Gao, Q., Ma, Y., Yang, S., Yin, M., Yu, M., Fang, C., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14483 · Cited by 15
Metadata
- Authors
- Hill, R. A., Tong, L., Yuan, P., Murikinati, S., Gupta, S., & Grutzendler, J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 87
- Issue
- 1
- Pages
- 95-110
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1540025214
- Cited by
- 722
- References
- 15
- FWCI
- 25.39
- Type
- journal article
- Language
- en
- Open access
- bronze
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