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. Nielson, A.A. Berthiaume, S.K. Bonney, A.Y. Shih. (2022) Frontiers in Neuroscience. 16:974311. LINK

Reinforced thinned-skull window for repeated imaging of the neonatal mouse brain. V. Coelho-Santos, T. Tieu, A.Y. Shih. (2022) Neurophotonics. 9(3):031918. LINK

Antibody-based in vivo leukocyte label for two-photon brain imaging in mice. Faulhaber LD, D’Costa O, Shih AY, Gust J. (2022) Neurophotonics. 9(3):031917. 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 PhysiologyPDF

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


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