Andy Y. Shih

Title
InstitutionMedical University of South Carolina
DepartmentNeuroscience
AddressP.O. Box MSC 323
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    Our lab is interested in understanding how blood is supplied to the brain during health and disease. We use advanced optical techniques and genetic targeting strategies to visualize and manipulate blood flow at the level of the smallest arterioles, venules and capillaries of the brain. The goal is to determine how anomalies in blood flow at the microvascular level affect brain function and repair after injury. Our current research is driven by three main questions.

    1) What microvascular changes occur in the chronic stages of stroke, and how do those changes affect neuronal rewiring during rehabilitation?

    2) What vascular dysfunctions are involved in cognitive impairment during dementia, and can we advance imaging techniques to detect them in humans?

    3) How is cortical blood flow is regulated by the electrical, ionic and modulatory activity of the underlying neurons and nonneuronal cells?

    Our research is expected to advance our understanding and treatment of vascular diseases in human subjects including stroke and vascular dementia. It is also expected to impact measurement of brain function and detection of microvascular lesions by non-invasive imaging techniques such as MRI.

    Please visit our website for more information: www.theshihlab.com
    Collapse keywords
    neuroscience, microvascular change, vascular dysfunction

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Ornelas S, Berthiaume AA, Bonney SK, Coelho-Santos V, Underly RG, Kremer A, Guérin CJ, Lippens S, Shih AY. Three-dimensional ultrastructure of the brain pericyte-endothelial interface. J Cereb Blood Flow Metab. 2021 May 10; 271678X211012836. PMID: 33970018.
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    2. Yan W, Siegert RJ, Zhou H, Zou X, Wu L, Luo X, Li T, Huang Y, Guan H, Chen X, Mao M, Xia K, Zhang L, Li E, Li C, Zhang X, Zhou Y, Shih A, Fombonne E, Zheng Y, Han J, Sun Z, Jiang YH, Wang Y. Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis. Autism. 2021 Apr 12; 13623613211004054. PMID: 33845648.
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    3. Liao FF, Lin G, Chen X, Chen L, Zheng W, Raghow R, Zhou FM, Shih AY, Tan XL. Endothelial Nitric Oxide Synthase-Deficient Mice. Am J Pathol. 2021 Mar 10. PMID: 33711310.
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    4. McDowell KP, Berthiaume AA, Tieu T, Hartmann DA, Shih AY. VasoMetrics: unbiased spatiotemporal analysis of microvascular diameter in multi-photon imaging applications. Quant Imaging Med Surg. 2021 Mar; 11(3):969-982. PMID: 33654670.
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    5. Hartmann DA, Berthiaume AA, Grant RI, Harrill SA, Koski T, Tieu T, McDowell KP, Faino AV, Kelly AL, Shih AY. Brain capillary pericytes exert a substantial but slow influence on blood flow. Nat Neurosci. 2021 May; 24(5):633-645. PMID: 33603231.
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    6. Rayner SG, Howard CC, Mandrycky CJ, Stamenkovic S, Himmelfarb J, Shih AY, Zheng Y. Multiphoton-Guided Creation of Complex Organ-Specific Microvasculature. Adv Healthc Mater. 2021 05; 10(10):e2100031. PMID: 33586357.
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    7. Underly RG, Shih AY. Rapid, Nitric Oxide Synthesis-Dependent Activation of MMP-9 at Pericyte Somata During Capillary Ischemia in vivo. Front Physiol. 2020; 11:619230. PMID: 33505320.
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    8. Carare RO, Aldea R, Agarwal N, Bacskai BJ, Bechman I, Boche D, Bu G, Bulters D, Clemens A, Counts SE, de Leon M, Eide PK, Fossati S, Greenberg SM, Hamel E, Hawkes CA, Koronyo-Hamaoui M, Hainsworth AH, Holtzman D, Ihara M, Jefferson A, Kalaria RN, Kipps CM, Kanninen KM, Leinonen V, McLaurin J, Miners S, Malm T, Nicoll JAR, Piazza F, Paul G, Rich SM, Saito S, Shih A, Scholtzova H, Snyder H, Snyder P, Thormodsson FR, van Veluw SJ, Weller RO, Werring DJ, Wilcock D, Wilson MR, Zlokovic BV, Verma A. Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-ß from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy. Alzheimers Dement (Amst). 2020; 12(1):e12053. PMID: 32775596.
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    9. Zhou H, Xu X, Yan W, Zou X, Wu L, Luo X, Li T, Huang Y, Guan H, Chen X, Mao M, Xia K, Zhang L, Li E, Ge X, Zhang L, Li C, Zhang X, Zhou Y, Ding D, Shih A, Fombonne E, Zheng Y, Han J, Sun Z, Jiang YH, Wang Y. Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years. Neurosci Bull. 2020 Sep; 36(9):961-971. PMID: 32607739.
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    10. Watson AN, Berthiaume AA, Faino AV, McDowell KP, Bhat NR, Hartmann DA, Shih AY. Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRß+/- mice. J Cereb Blood Flow Metab. 2020 12; 40(12):2387-2400. PMID: 31987006.
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    11. O'Herron P, Summers PM, Shih AY, Kara P, Woodward JJ. In vivo two-photon imaging of neuronal and brain vascular responses in mice chronically exposed to ethanol. Alcohol. 2020 06; 85:41-47. PMID: 31857103.
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    12. Sorond FA, Whitehead S, Arai K, Arnold D, Carmichael ST, De Carli C, Duering M, Fornage M, Flores-Obando RE, Graff-Radford J, Hamel E, Hess DC, Ihara M, Jensen MK, Markus HS, Montagne A, Rosenberg G, Shih AY, Smith EE, Thiel A, Tse KH, Wilcock D, Barone F. Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging. Geroscience. 2020 02; 42(1):81-96. PMID: 31811528.
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    13. Coelho-Santos V, Shih AY. Postnatal development of cerebrovascular structure and the neurogliovascular unit. Wiley Interdiscip Rev Dev Biol. 2020 03; 9(2):e363. PMID: 31576670.
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    14. Berthiaume AA, Shih AY. Sharpening the tools for pericyte research. Nat Neurosci. 2019 07; 22(7):1041-1043. PMID: 31235904.
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    15. Guérin CJ, Kremer A, Borghgraef P, Shih AY, Lippens S. Combining serial block face and focused ion beam scanning electron microscopy for 3D studies of rare events. Methods Cell Biol. 2019; 152:87-101. PMID: 31326028.
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    16. Berthiaume AA, Hartmann DA, Majesky MW, Bhat NR, Shih AY. Pericyte Structural Remodeling in Cerebrovascular Health and Homeostasis. Front Aging Neurosci. 2018; 10:210. PMID: 30065645.
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    17. Shih AY, Hyacinth HI, Hartmann DA, van Veluw SJ. Rodent Models of Cerebral Microinfarct and Microhemorrhage. Stroke. 2018 03; 49(3):803-810. PMID: 29459393.
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    18. Berthiaume AA, Grant RI, McDowell KP, Underly RG, Hartmann DA, Levy M, Bhat NR, Shih AY. Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain. Cell Rep. 2018 01 02; 22(1):8-16. PMID: 29298435.
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    19. Hartmann DA, Hyacinth HI, Liao FF, Shih AY. Does pathology of small venules contribute to cerebral microinfarcts and dementia? J Neurochem. 2018 03; 144(5):517-526. PMID: 28950410.
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    20. Mateo C, Knutsen PM, Tsai PS, Shih AY, Kleinfeld D. Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent "Resting-State" Connectivity. Neuron. 2017 Nov 15; 96(4):936-948.e3. PMID: 29107517.
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    21. Grant RI, Hartmann DA, Underly RG, Berthiaume AA, Bhat NR, Shih AY. Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex. J Cereb Blood Flow Metab. 2019 03; 39(3):411-425. PMID: 28933255.
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    22. Hyacinth HI, Sugihara CL, Spencer TL, Archer DR, Shih AY. Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease. J Cereb Blood Flow Metab. 2019 02; 39(2):342-351. PMID: 28925802.
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    23. van Veluw SJ, Shih AY, Smith EE, Chen C, Schneider JA, Wardlaw JM, Greenberg SM, Biessels GJ. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 2017 09; 16(9):730-740. PMID: 28716371.
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    24. Underly RG, Shih AY. Photothrombotic Induction of Capillary Ischemia in the Mouse Cortex during in vivo Two-photon Imaging. Bio Protoc. 2017 Jul 05; 7(13). PMID: 28835908.
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    25. McKinnon ET, Fridriksson J, Glenn GR, Jensen JH, Helpern JA, Basilakos A, Rorden C, Shih AY, Spampinato MV, Bonilha L. Structural plasticity of the ventral stream and aphasia recovery. Ann Neurol. 2017 Jul; 82(1):147-151. PMID: 28628946.
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    26. Summers PM, Hartmann DA, Hui ES, Nie X, Deardorff RL, McKinnon ET, Helpern JA, Jensen JH, Shih AY. Functional deficits induced by cortical microinfarcts. J Cereb Blood Flow Metab. 2017 Nov; 37(11):3599-3614. PMID: 28090802.
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    27. Underly RG, Levy M, Hartmann DA, Grant RI, Watson AN, Shih AY. Pericytes as Inducers of Rapid, Matrix Metalloproteinase-9-Dependent Capillary Damage during Ischemia. J Neurosci. 2017 01 04; 37(1):129-140. PMID: 28053036.
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    28. Taylor ZJ, Hui ES, Watson AN, Nie X, Deardorff RL, Jensen JH, Helpern JA, Shih AY. Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex. J Cereb Blood Flow Metab. 2016 08; 36(8):1357-73. PMID: 26661182.
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    29. Hartmann DA, Underly RG, Grant RI, Watson AN, Lindner V, Shih AY. Pericyte structure and distribution in the cerebral cortex revealed by high-resolution imaging of transgenic mice. Neurophotonics. 2015 Oct; 2(4):041402. PMID: 26158016.
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    30. Shih AY, Rühlmann C, Blinder P, Devor A, Drew PJ, Friedman B, Knutsen PM, Lyden PD, Mateo C, Mellander L, Nishimura N, Schaffer CB, Tsai PS, Kleinfeld D. Robust and fragile aspects of cortical blood flow in relation to the underlying angioarchitecture. Microcirculation. 2015 Apr; 22(3):204-218. PMID: 25705966.
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    31. Hartmann DA, Underly RG, Watson AN, Shih AY. A murine toolbox for imaging the neurovascular unit. Microcirculation. 2015 Apr; 22(3):168-82. PMID: 25352367.
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    32. Shih AY, Nishimura N, Nguyen J, Friedman B, Lyden PD, Schaffer CB, Kleinfeld D. Optically induced occlusion of single blood vessels in rodent neocortex. Cold Spring Harb Protoc. 2013 Dec 01; 2013(12):1153-60. PMID: 24298038.
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    33. Taylor ZJ, Shih AY. Targeted Occlusion of Individual Pial Vessels of Mouse Cortex. Bio Protoc. 2013 Sep 05; 3(17). PMID: 27547784.
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    34. Driscoll JD, Shih AY, Drew PJ, Cauwenberghs G, Kleinfeld D. Two-photon imaging of blood flow in the rat cortex. Cold Spring Harb Protoc. 2013 Aug 01; 2013(8):759-67. PMID: 23906919.
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    35. Shih AY, Blinder P, Tsai PS, Friedman B, Stanley G, Lyden PD, Kleinfeld D. The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit. Nat Neurosci. 2013 Jan; 16(1):55-63. PMID: 23242312.
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    36. Shih AY, Mateo C, Drew PJ, Tsai PS, Kleinfeld D. A polished and reinforced thinned-skull window for long-term imaging of the mouse brain. J Vis Exp. 2012 Mar 07; (61). PMID: 22433225.
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    37. Shih AY, Driscoll JD, Drew PJ, Nishimura N, Schaffer CB, Kleinfeld D. Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. J Cereb Blood Flow Metab. 2012 Jul; 32(7):1277-309. PMID: 22293983.
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    38. Drew PJ, Shih AY, Kleinfeld D. Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. Proc Natl Acad Sci U S A. 2011 May 17; 108(20):8473-8. PMID: 21536897.
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    39. Kleinfeld D, Blinder P, Drew PJ, Driscoll JD, Muller A, Tsai PS, Shih AY. A guide to delineate the logic of neurovascular signaling in the brain. Front Neuroenergetics. 2011; 3:1. PMID: 21559095.
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    40. Driscoll JD, Shih AY, Iyengar S, Field JJ, White GA, Squier JA, Cauwenberghs G, Kleinfeld D. Photon counting, censor corrections, and lifetime imaging for improved detection in two-photon microscopy. J Neurophysiol. 2011 Jun; 105(6):3106-13. PMID: 21471395.
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    41. Drew PJ, Shih AY, Driscoll JD, Knutsen PM, Blinder P, Davalos D, Akassoglou K, Tsai PS, Kleinfeld D. Chronic optical access through a polished and reinforced thinned skull. Nat Methods. 2010 Dec; 7(12):981-4. PMID: 20966916.
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    42. Valmianski I, Shih AY, Driscoll JD, Matthews DW, Freund Y, Kleinfeld D. Automatic identification of fluorescently labeled brain cells for rapid functional imaging. J Neurophysiol. 2010 Sep; 104(3):1803-11. PMID: 20610792.
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    43. Blinder P, Shih AY, Rafie C, Kleinfeld D. Topological basis for the robust distribution of blood to rodent neocortex. Proc Natl Acad Sci U S A. 2010 Jul 13; 107(28):12670-5. PMID: 20616030.
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    44. Weidemann A, Kerdiles YM, Knaup KX, Rafie CA, Boutin AT, Stockmann C, Takeda N, Scadeng M, Shih AY, Haase VH, Simon MC, Kleinfeld D, Johnson RS. The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. J Clin Invest. 2009 Nov; 119(11):3373-83. PMID: 19809162.
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    45. Drew PJ, Blinder P, Cauwenberghs G, Shih AY, Kleinfeld D. Rapid determination of particle velocity from space-time images using the Radon transform. J Comput Neurosci. 2010 Aug; 29(1-2):5-11. PMID: 19459038.
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    46. Friedman B, Schachtrup C, Tsai PS, Shih AY, Akassoglou K, Kleinfeld D, Lyden PD. Acute vascular disruption and aquaporin 4 loss after stroke. Stroke. 2009 Jun; 40(6):2182-90. PMID: 19372455.
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    47. Shih AY, Friedman B, Drew PJ, Tsai PS, Lyden PD, Kleinfeld D. Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke. J Cereb Blood Flow Metab. 2009 Apr; 29(4):738-51. PMID: 19174826.
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    48. Shih AY, Erb H, Murphy TH. Dopamine activates Nrf2-regulated neuroprotective pathways in astrocytes and meningeal cells. J Neurochem. 2007 Apr; 101(1):109-19. PMID: 17394461.
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    49. Pacchioni AM, Vallone J, Melendez RI, Shih A, Murphy TH, Kalivas PW. Nrf2 gene deletion fails to alter psychostimulant-induced behavior or neurotoxicity. Brain Res. 2007 Jan 05; 1127(1):26-35. PMID: 17113054.
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    50. Shih AY, Erb H, Sun X, Toda S, Kalivas PW, Murphy TH. Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci. 2006 Oct 11; 26(41):10514-23. PMID: 17035536.
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    51. Sun X, Shih AY, Johannssen HC, Erb H, Li P, Murphy TH. 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. J Biol Chem. 2006 Jun 23; 281(25):17420-17431. PMID: 16624809.
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    52. Shih AY, Fernandes HB, Choi FY, Kozoriz MG, Liu Y, Li P, Cowan CM, Klegeris A. Policing the police: astrocytes modulate microglial activation. J Neurosci. 2006 Apr 12; 26(15):3887-8. PMID: 16611803.
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    53. Shih AY, Li P, Murphy TH. A small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against cerebral ischemia in vivo. J Neurosci. 2005 Nov 02; 25(44):10321-35. PMID: 16267240.
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    54. Shih AY, Imbeault S, Barakauskas V, Erb H, Jiang L, Li P, Murphy TH. Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem. 2005 Jun 17; 280(24):22925-36. PMID: 15840590.
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    55. Lee JM, Shih AY, Murphy TH, Johnson JA. NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem. 2003 Sep 26; 278(39):37948-56. PMID: 12842875.
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    56. Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH. Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci. 2003 Apr 15; 23(8):3394-406. PMID: 12716947.
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