RECENT HIGHLIGHTS
Deep Imaging to Dissect Microvascular Contributions to White Matter Degeneration in Rodent Models of Dementia. S. Stamenkovic, Y. Li, J. Waters, A.Y. Shih (2023) Stroke. 54(5):1403-1415. LINK
The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association. C. Iadecola, E.E. Smith, J. Anrather, C. Gu, A. Mishra, S. Misra, M.A. Perez-Pinzon, A.Y. Shih, F.A. Sorond, S.J. van Veluw, C.L. Wellington (2023) Stroke. Online ahead of print. LINK
Deficiency in pericyte remodeling as a basis for impaired capillary flow and structure during brain aging. A.A. Berthiaume, F. Schmid, S. Stamenkovic, V. Coelho-Santos, C. Nielson, B. Weber, M.W. Majesky, and A.Y. Shih. (2022) Nature Communications. 7;13(1):5912. LINK
Precise, 3-D optogenetic control of the diameter of single arterioles. P.J. O’Herron, D.A. Hartmann, K. Xie, P. Kara, A.Y. Shih. (2022) Elife. 11:e72802. LINK
INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury. B. Calabrese, S. Jones, Y. Yamaguchi-Shiraishi, M. Lingelbach, U. Manor, T.M. Svitkina, H.N. Higgs, A.Y. Shih, and S. Halpain. (2022) Nature Communications. 13(1):6037. LINK
In vivo single cell optical ablation of brain pericytes. C.D. Frontiers in Neuroscience. 16:974311. LINK
Reinforced thinned-skull window for repeated imaging of the neonatal mouse brain. V. LINK
Public volume electron microscopy data: A rich resource to study brain microvasculature. S.K. Bonney, V. Coelho-Santos, S.F. Huang, M. Takeno, J. Kornfeld, A. Keller, A.Y. Shih. (2022). Frontiers in Cellular and Developmental Biology. 10:849469. LINK
Brain capillary obstruction as a novel mechanism of anti-CD19 CAR T cell neurotoxicity. L.D. Faulhaber, A.Q. Phuong, K.J. Hartsuyker, Y. Cho, K.K. Mand, S.D. Harper, A.K. Olson, G.A. Garden, and A.Y. Shih, and J. Gust. (2021). Brain Communications. 4(1):fcab309. LINK
Distinct features of brain perivascular fibroblasts and mural cells revealed by in vivo two-photon imaging. S.K. Bonney, L.T. Sullivan, T.J. Cherry, R. Daneman, and A.Y. Shih (2021). JCBFM. 42(6):966-978. PDF
Pericyte control of blood flow across microvascular zones in the central nervous system. D.A. Hartmann, V. Coelho-Santos, and A.Y. Shih (2021). Annual Reviews of Physiology. PDF
Imaging the Construction of Capillary Networks in the Neonatal Mouse Brain. V. Coelho-Santos, A.A. Berthiaume, S. Ornelas, H. Stuhlmann, and A.Y. Shih (2021). PNAS. LINK PDF NEWS & VIEWS headmount plans
Three-dimensional ultrastructure of the brain pericyte-endothelial interface. S. Ornelas, A.A. Berthiaume, S.K. Bonney, V. Coelho-Santos, R.G. Underly, A. Kremer, C.J. Guérin, S. Lippens, and A.Y. Shih (2021). JCBFM. 41(9):2185-2200. PDF
Brain capillary pericytes exert a substantial but slow influence on blood flow. D.A. Hartmann, A.A. Berthiaume, R.I. Grant, S.A. Harill, T. Koski, T. Tieu, K.P. McDowell, A.V. Faino, A. Kelly, and A.Y. Shih (2021). Nature Neuroscience. 24(5):633-645. PDF MEDIA NEWS & VIEWS
PRIOR STUDIES
Cerebral Microinfarcts
Rodent models of cerebral microinfarct and microhemorrhage. A.Y. Shih, H.I. Hyacinth, D.A. Hartmann, S.J. van Veluw. Stroke (2018). Epub ahead of print. PDF
Does the pathology of small venules contribute to cerebral microinfarcts and dementia? D.A. Hartmann, H.I. Hyacinth, F.F. Liao and AY. Shih. Journal of Neurochemistry (2017). 144(5):517-526. PDF
Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease. H.I. Hyacinth, C.L. Sugihara, T.L. Spencer, D.R. Archer, A.Y. Shih (2017). Journal of Cerebral Blood Flow and Metabolism. Epub ahead of print. PDF & Supplement.
Detection, risk factors, and functional consequences of cerebral microinfarcts. S.J. van Veluw, A.Y. Shih, E.E. Smith, C. Chen, J.A. Schneider, J.M. Wardlaw, S.M. Greenberg, G.J. Biessels. Lancet Neurology (2017). 4422(17)30196-5. Review. PDF
Functional deficits induced by cortical microinfarcts. P. M. Summer; D. A. Hartman; E. S. Hu; X. Nie; R. L. Deardorff; E. T. McKinnon; J. A. Helpern; J. H. Jensen; A. Y. Shih. Journal of Cerebral Blood Flow and Metabolism (2017). 37(11):3599-3614 PDF & Supplement
Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex. Z. J. Taylor, E. S. Hui, A. N. Watson, X. Nie, R. L. Deardorff, J. H. Jensen, J. A. Helpern and A. Y. Shih. Journal of Cerebral Blood Flow and Metabolism (2016). Aug;36(8):1357-73. PDF & Supplement
Robust and fragile aspects of cortical blood flow in relation to the underlying angioarchitecture. A. Y. Shih*, C. Rühlmann*, P. Blinder, A. Devor, P. J. Drew. B. Friedman, P. M. Knutsen, P. D. Lyden, C. Mateo, L. Mellander N. Nishimura, C. B. Schaffer, P. S. Tsai and D. Kleinfeld (2014). Microcirculation. 22(3): 204–218. PDF
Targeted occlusion of individual pial vessels of mouse cortex. Z. J. Taylor and A.Y. Shih (2013). Bio-protocols. Web Resource
The smallest stroke: Occlusion of one penetrating vessel leads to microinfarction and a cognitive deficit. A.Y. Shih, P. Blinder, B. Friedman, P.S. Tsai, G.M. Stanley, P.D. Lyden, D. Kleinfeld (2013). Nature Neuroscience. 16(1):55-63. PDF & Supplement
Topological basis for the robust distribution of blood to rodent neocortex. P. Blinder *, A.Y. Shih *, C.A. Rafie, and D. Kleinfeld (2010). Proceedings of the National Academy of Sciences. 107(28): 12670-5. (* equal co-first authors). PDF & Supplement
Imaging of Brain Microvessels
Rapid, nitric oxide synthesis-dependent activation of MMP-9 at pericyte somata during capillary ischemia in vivo. R.G. Underly, A.Y. Shih (2020) Frontiers in Physiology. 11:619230. LINK
Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRbeta+/- mice. A.N. Watson, A.A. Berthiaume, A.V. Faino, K.P. McDowell, N.R. Bhat, D.A. Hartmann, and A.Y. Shih (2020). Journal of Cerebral Blood Flow and Metabolism. Jan 27, Early online. PDF
Postnatal development of cerebrovascular structure and the neurogliovascular unit. V. Coelho-Santos and A.Y. Shih (2019). WIRES Developmental Biology.9(2):e363 PDF
Sharpening the tools for pericyte research. A.A Berthiaume and A.Y. Shih (2019). Nature Neuroscience. 22: 1041–1043. PDF A News and Views article for Pericyte loss leads to circulatory failure and pleiotropin depletion causing neuronal loss by Nikolakopoulou et al. (2019). Nature Neuroscience. 22: 1089–1098.
Pericyte structural remodeling in cerebrovascular health and homeostasis. A.A. Berthiaume, D.A. Hartmann, M.W. Majesky, N.R. Bhat and A.Y. Shih (2018). Frontiers in Aging Neuroscience. Volume: Article 210. PDF
Dynamic remodeling of pericytes in vivo maintains capillary coverage in the adult mouse brain. A.A. Berthiaume, R.I. Grant, K.P. McDowell, R.G. Underly, D.A. Hartmann, M. Levy, N.R. Bhat and A.Y. Shih (2018). Cell Reports. 22(1):8-16. PDF
Entrainment of arteriole vasomotor fluctuations by neural activity is a basis of blood-oxygen-level-dependent “resting state” connectivity. C. Mateo, P.M. Knutsen, P.S. Tsai, A.Y. Shih and D. Kleinfeld (2017). Neuron. 96(4):936-948. PDF & Commentary
Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex. R.I. Grant, D.A. Hartmann, R.G. Underly, A.A. Berthiaume, N.R. Bhat and A.Y. Shih (2017). Journal of Cerebral Blood Flow and Metabolism. 39(3):411-425. PDF & Supplement & Supplemental Video
Pericytes as inducers of rapid, matrix metalloproteinase-9-dependent capillary damage during ischemia. R. G. Underly; M. Levy; D. A. Hartmann; R. I. Grant; A. N. Watson; A. Y. Shih (2017). The Journal of Neuroscience. 37(1):129-140. PDF
Pericyte structure and distribution in the cerebral cortex revealed by high-resolution imaging of transgenic mice. D. A. Hartmann; R. G. Underly; R. I. Grant; A. N. Watson; V. Lindner; A. Y. Shih (2015). Neurophotonics. 2(4), 041402 (May 27, 2015). PDF
A murine toolbox for imaging the neurovascular unit. D. A. Hartmann, R. G. Underly, A. N. Watson, A.Y. Shih (2015). Microcirculation. 22(3): 168–182. PDF
Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. P.J. Drew, A.Y. Shih, D. Kleinfeld (2011). Proceedings of the National Academy of Sciences. 108(20): 8473-98. PDF & Supplement
A guide to delineate the logic of neurovascular signaling in the brain. D. Kleinfeld, P. Blinder, P. J. Drew, J.D. Driscoll, A. Muller, P.S. Tsai, A.Y. Shih. (2011) Frontiers in Neuroenergetics. 2011. 3:1. PDF
Stroke Injury and Recovery
Rapid, nitric oxide synthesis-dependent activation of MMP-9 at pericyte somata during capillary ischemia in vivo. R.G. Underly, A.Y. Shih (2020) Frontiers in Physiology (in press). LINK
Pericytes as inducers of rapid, matrix metalloproteinase-9-dependent capillary damage during ischemia. R. G. Underly; M. Levy; D. A. Hartmann; R. I. Grant; A. N. Watson; A. Y. Shih (2017). The Journal of Neuroscience. 37(1):129-140. PDF
Structural plasticity of the ventral stream and aphasia recovery. E.T. McKinnon, J. Fridriksson, G.R. Glenn, J.H. Jensen, J.A. Helpern, A. Basilakos, C. Rorden. A.Y. Shih, M.V. Spampinato, L. Bonilha. Annals of Neurology. 2017 Jul;82(1):147-151. PDF
Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke. A. Y. Shih, B. Friedman, P. J. Drew, P. S. Tsai, P. D. Lyden and D. Kleinfeld (2009). Journal of Cerebral Blood Flow and Metabolism. 29: 738-751. PDF & Supplement
Glial response is an essential component of hypoxia-induced erythropoiesis. A. Weidemann, K. X. Knaup, C. A. Rafie, A. T. Boutin, C. Stockmann, N. Takeda, M. Scadeng, A. Y. Shih, V. H. Haase, M. C. Simon, D. Kleinfeld, and R. S. Johnson (2009). Journal of Clinical Investigation. 119(11):3373-83. PDF & Supplement
Acute vascular disruption and Aquaporin 4 loss after stroke. B. Friedman, C. Schachtrup, P.S. Tsai, A.Y. Shih, K. Akassoglou, D. Kleinfeld, and P.D. Lyden (2009). Stroke. 40: 2182-2190. PDF
Dopamine activates Nrf2-regulated neuroprotective pathways in astrocytes and meningeal cells. A.Y. Shih, H. Erb, T.H. Murphy (2007). Journal of Neurochemistry.101(1):109-19. PDF
Nrf2 gene deletion fails to alter psychostimulant-induced behavior or neurotoxicity. A.M. Pacchioni, J. Vallone, R.I. Melendez, A.Y. Shih, T.H. Murphy, P.W. Kalivas (2007). Brain Research.1127(1):26-35. PDF
Cystine/glutamate exchange modulates glutathione supply for cell proliferation and neuroprotection from oxidative stress. A.Y. Shih, H. Erb, X. Sun, X. Toda, P.W. Kalivas, T.H. Murphy (2006). Journal of Neuroscience. 26(41):10514-23. PDF
Policing the police: astrocytes modulate microglial activation. A.Y. Shih, H.B. Fernandes, F.Y. Choi, M.G. Kozoriz, Y. Liu, P. Li. C.M. Cowan, A. Klegeris (2006). Journal of Neuroscience. 26(15): 3887-3888. PDF
Two-photon imaging of glutathione levels in intact brain indicates enhanced redox buffering in developing neurons and cells at the cerebrospinal fluid and blood-brain interface. X. Sun, A.Y. Shih, H.C. Johannssen, H. Erb, P. Li, T.H. Murphy (2006). Journal of Biological Chemistry. 281(25):17420-17431. PDF
A small molecule inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. A.Y. Shih, P. Li and T.H. Murphy (2005). Journal of Neuroscience.25(44):10321-10335. PDF
Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. A.Y. Shih*, S. Imbeault *, V. Barakauskas, H. Erb, L. Jiang, P. Li, T.H. Murphy (2005). Journal of Biological Chemistry. 280(24): 22925-22936. (* equal co-first authors). PDF
NF-E2-related factor 2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J.M. Lee, A.Y. Shih, T.H. Murphy, J.A. Johnson (2003). Journal of Biological Chemistry.278(39):37948-56. PDF
Coordinate regulation of glutathione biosynthesis and release by Nrf2 expressing glia potently protects neurons from oxidative stress. A.Y. Shih, D.A. Johnson, G. Wong, A.D. Kraft, L. Jiang, H. Erb, J.A. Johnson and T.H. Murphy (2003). The Journal of Neuroscience. 23 (8):3394-406. PDF
xCT cystine transporter expression in HEK293 cells: pharmacology and localization. A.Y. Shih and T.H. Murphy (2001). Biochemical and Biophysical Reseasrch Communications. 282(5):1132-7. PDF
Two-photon Imaging Methods
Multiphoton-Guided Creation of Complex Organ-Specific Microvasculature. S.G. Rayner, C.C Howard, C.J. Mandrycky, S. Stamenkovic, J. Himmelfarb, A.Y. Shih, Y. Zheng. (2021) Advanced Healthcare Materials. LINK
VasoMetrics: Unbiased Spatiotemporal Analysis of Microvascular Diameter in Multi-photon Imaging Applications. K.P. McDowell, A.A. Berthiaume, T. Tieu, D.A. Hartmann, and A.Y. Shih (2020). Quantitative Imaging in Medicine and Surgery (in press). PDF
Photothrombotic induction of capillary ischemia in the mouse cortex during in vivo two-photon imaging. R.G. Underly and A.Y. Shih (2017). Bio-protocol. Web Resource.
Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. Schaffer, D. Kleinfeld (2012). Journal of Cerebral Blood Flow and Metabolism. 32: 1277-1309. PDF
A polished and reinforced thinned skull window for long-term imaging of the mouse brain. A. Y. Shih, C. Mateo, P. J. Drew, P.S.Tsai, D. Kleinfeld (2012). Journal of Visualized Experiments. Mar 7;(61). PDF
Photon counting, censor corrections, and lifetime imaging for improved detection in two-photon microscopy. J. D. Driscoll, A.Y. Shih, G.A. White, Q.-T. Nguyen, P.S. Tsai, J.A. Squier, G. Cauwenberghs, D. Kleinfeld (2011). Journal of Neurophysiology. 105(6): 3106-13. PDF
Chronic optical access through a polished and reinforced thinned skull. P.J. Drew, A.Y. Shih, P.S. Tsai, P. Knutsen, D. Davalos, P. Blinder, K. Akassoglou, and D. Kleinfeld (2010). Nature Methods. 7(12): 981-4. (Selected for cover image). PDF & Supplement
Automatic identification of fluorescently labeled brain cells for rapid functional imaging. I. Valmianski, A. Y. Shih, J. D. Driscoll, D. M. Matthews, Y. Freund and D. Kleinfeld (2010). Journal of Neurophysiology. 104(3): 1803-11. PDF & Supplement
Rapid determination of particle velocity from space-time images using the Radon transform. P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih and D. Kleinfeld (2010). Journal of Computational Neuroscience (2010) 29:5-11. PDF
Book Chapters
In vivo optical imaging and manipulation of brain pericytes. A.A. Berthiaume, V. Coelho-Santos, D.A. Hartmann, and A.Y. Shih (2020). Biology of Pericytes – Recent Advances. Book Chapter. Editor: Alexander Birbrair. In press. PDF
Combining serial block face and focused ion beam scanning electron microscopy for 3D studies of rare events. C.J. Guerin, A. Kremer, P. Borghgraef, A.Y. Shih, S. Lippens. In Methods in Cell Biology, Volume 152, 2019. PDF Movie
Two-photon imaging of cerebral vasodynamics in awake mice during health and disease. P.M. Summers, Z.J. Taylor and A.Y. Shih. In Intravital Microscopy. Roberto Weigert, ed., 2014, Springer Science and Business Media. PDF
Imaging vasodynamics in the awake mouse brain with two-photon microscopy. A. Y. Shih, P.J. Drew and David Kleinfeld (2013). In Neurovascular Coupling Methods. Theodore H. Schwartz and Wolfgang Walz, eds., 2013, Springer Science and Business Media, Chapter 4. PDF
Two-photon microscopy to measure blood flow and concurrent brain cell activity. A. Y. Shih, J. D. Driscoll, M.J. Pesavento, D. Kleinfeld (2012). B. Weber and F. Helmchen, eds., 2012, Elsevier, NY, Chapter 3.3 PDF
Optical-based models of single vessel occlusion in rodent neocortex. A. Y. Shih, N. Nishimura, J. Nguyen, B. Friedman, P. D. Lyden, C. B. Schaffer, and D. Kleinfeld. In Imaging in Neuroscience: A Laboratory Manual (Book 2), F. Helmchen and A. Konnerth, editors, R. Yuste, series editor, 2011, Cold Spring Harbor Laboratory Press, NY, Chapter 85, 939-948. PDF
Quantitative two-photon imaging of blood flow in cortex. J. D. Driscoll, A. Y. Shih, P. J. Drew, P.J. Drew, I. Valmianski, and D. Kleinfeld. In Imaging in Neuroscience: A Laboratory Manual (Book 2), F. Helmchen and A. Konnerth, editors, R. Yuste, series editor, 2011, Cold Spring Harbor Laboratory Press, NY, Chapter 84, 927-938. PDF
Statics and dynamics of the angiome probed by two-photon laser scanning microscopy under normal conditions and following experimental stroke. A. Devor, A. Y. Shih, P. S. Tsai, P. Blinder, P. Tian, and D. Kleinfeld. In Imaging the Brain with Optical Methods, A. Roe, editor, 2008, Springer Press. PDF
Targeted occlusion to surface and deep vessels in neocortex via linear and nonlinear optical absorption. D. Kleinfeld, B. Friedman, P. D. Lyden, and A. Y. Shih. In Animal Models of Acute Neurological Injuries, J. Chen, Z. Xu, X.-M. Xu and J. Zhang, editors, 2008, Contemporary Neuroscience Series, The Humana Press. PDF