CD47 as a neurovascular target for stroke therapy

Summary

Principal Investigator: ENG LO
Abstract: The concept of the neurovascular unit suggests that, to be successful, stroke therapy must target both vascular and neuronal compartments. Here, we propose that the transmembrane receptor CD47 (also known as integrin associated protein) may be an ideal neurovascular target for stroke therapy. Pilot data suggest that (i) the major CD47 ligand thrombospondin-1 (TSP-1) is elevated in plasma of acute stroke patients within 8 hrs, (ii) CD47 and its ligands signal regulatory protein (SIRP-a) and TSP-1 are upregulated in cerebral endothelial cells and neurons after injury, (iii) activation of CD47 in cerebral endothelial cells upregulates inflammatory adhesion molecules (ICAM-1, VCAM-1), (iv) activation of CD47 induces cell death in both neurons and cerebral endothelial cells, and (v) CD47 is upregulated in brain after focal cerebral ischemia, and CD47 knockout mice may have smaller infarcts and reduced neutrophil infiltration compared to wildtype mice. Therefore, we propose the overall hypothesis that CD47 mediates inflammation and cell death in both vascular and neuronal compartments after stroke. In Aim 1, we will use cerebral endothelial cell cultures to show that activation of CD47 upregulates inflammatory mediators (MMP-9, ICAM-1, VCAM-1) and induces cell death. Oxidative stress via AP-1 and NFkB responses will be assesed as a trigger for CD47 upregulation. Interactions with the two major CD47 ligands TSP-1 and SIRP-a will be examined. Signaling specificity will be assessed using cells derived from knockout mice lacking either CD47 or the related receptor CD36. In Aim 2, we will use neuronal cultures to show that CD47 mediates cell death by triggering stress activated protein kinase cascades of p38 and JNK leading to caspase-dependent and/or caspase-independent cell death. Once again, we examine interactions between TSP-1 and SIRP-a, and use neurons from knockout mice to examine specific roles of CD47 versus CD36. In Aim 3, we will use a mouse model of focal cerebral ischemia to document the role of CD47 in neurovascular injury in vivo. Knockout mice lacking either TSP-1, CD47 or CD36 will be compared against wildtype mice. To distinguish blood versus tissue CD47 responses, we will also use bone marrow transplants to create chimeric mice. We aim to show that CD47 mediates neurovascular inflammation, blood-brain barrier leakage, and infarction after stroke. Proof-of-concept data collected here may lead to the development of CD47 as a novel neurovascular target for stroke therapy.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke
    Bing Qiao Zhao
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Stroke 38:748-52. 2007
  2. pmc Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats
    Kyung Pil Park
    Neuroprotection Research Laboratory, MGH East 149 2401 Charlestown, MA 02129, USA
    Stroke 40:2836-42. 2009
  3. ncbi Mechanisms and markers for hemorrhagic transformation after stroke
    A Rosell
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
    Acta Neurochir Suppl 105:173-8. 2008
  4. pmc Dysfunctional cell-cell signaling in the neurovascular unit as a paradigm for central nervous system disease
    Shuzhen Guo
    Neuroprotection Research Laboratory, MGH East 149 2401, 13th Street, Charlestown, MA 02129, USA
    Stroke 40:S4-7. 2009
  5. pmc Extension of the thrombolytic time window with minocycline in experimental stroke
    Yoshihiro Murata
    Neuroprotection Res Lab, Charlestown, MA 02129, USA
    Stroke 39:3372-7. 2008
  6. pmc Experimental model of warfarin-associated intracerebral hemorrhage
    Christian Foerch
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Masschusetts 02129, USA
    Stroke 39:3397-404. 2008
  7. ncbi Targeting extracellular matrix proteolysis for hemorrhagic complications of tPA stroke therapy
    Xiaoying Wang
    Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    CNS Neurol Disord Drug Targets 7:235-42. 2008
  8. pmc Protecting against cerebrovascular injury: contributions of 12/15-lipoxygenase to edema formation after transient focal ischemia
    Guang Jin
    Massachusetts General Hospital, Neuroprotection Research Laboratory, 149 13th Street, R 2401, Charlestown, MA 02129, USA
    Stroke 39:2538-43. 2008
  9. pmc Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons
    Shuzhen Guo
    Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
    Proc Natl Acad Sci U S A 105:7582-7. 2008
  10. ncbi Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke
    Elaine Besancon
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Trends Pharmacol Sci 29:268-75. 2008

Scientific Experts

  • Josephine M Lok
  • Ken Arai
  • ENG LO
  • Anna Rosell
  • Zhanyang Yu
  • Xiaoying Wang
  • Shuzhen Guo
  • Changhong Xing
  • Guang Jin
  • Stefanie Pallast
  • Klaus van Leyen
  • Kazuhide Hayakawa
  • Jianxiang Liu
  • Kyung Pil Park
  • Woo Jean Kim
  • Yoshihiro Murata
  • Sun Ryung Lee
  • Brian J Lee
  • Xiang Fan
  • Yong Guang Yang
  • Christian Foerch
  • Monique F Stins
  • Elaine Besancon
  • Ying Wei
  • Haihao Zhu
  • Katherine A Hajjar
  • Karen L Furie
  • Sunryung Lee
  • De Maw Chuang
  • Michael J Whalen
  • Young R Kim
  • Emiri Tejima
  • Robert H Scannevin
  • Kenneth J Rhodes
  • Bing Qiao Zhao
  • Nafiseh Alsharif
  • Seo Kyoung Hwang
  • Hyung Hwan Kim
  • Hwa Kyoung Shin
  • Tao Qin
  • Christian Waeber
  • James K Liao
  • Muge Yemisci
  • Angel T Som
  • Volker Brinkmann
  • Loc Duyen D Pham
  • Lai Ming Yung
  • Song Zhao
  • Kazim Yigitkanli
  • Anton Pekcec
  • Yasuhiro Egi
  • Ning Liu
  • Jie Lu
  • Chenggang Zhang
  • Ghislain Opdenakker
  • David G Nicholls
  • Yan Gao
  • Xunming Ji
  • Kiyoshi Tsuji
  • Hui Wang
  • MingMing Ning
  • Seoul Lee
  • Shoukat Dedhar
  • Joseph B Mandeville
  • Bing Hao Luo
  • Daniela Bermpohl
  • Jianhua Qiu
  • Zerong You
  • Maurits P A van Meer
  • Michael A Moskowitz
  • Niyati Mehta
  • Bruce R Rosen
  • Michael Tymianski
  • Sophia Wang
  • George Dai
  • Pradeep G Bhide
  • Bernhard Suter
  • Turgay Dalkara
  • Yoshi Murata
  • Maria Ericsson
  • Brian C Magliaro
  • Shu Zhen Guo

Detail Information

Publications39

  1. ncbi Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke
    Bing Qiao Zhao
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Stroke 38:748-52. 2007
    ..Acute versus chronic protease profiles within the neurovascular unit are likely to underlie critical responses to stroke, therapy, and recovery...
  2. pmc Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats
    Kyung Pil Park
    Neuroprotection Research Laboratory, MGH East 149 2401 Charlestown, MA 02129, USA
    Stroke 40:2836-42. 2009
    ..Here, we examined the temporal profiles of MMP-9 in blood and brain using a rat model of acute focal cerebral ischemia...
  3. ncbi Mechanisms and markers for hemorrhagic transformation after stroke
    A Rosell
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA, USA
    Acta Neurochir Suppl 105:173-8. 2008
    ....
  4. pmc Dysfunctional cell-cell signaling in the neurovascular unit as a paradigm for central nervous system disease
    Shuzhen Guo
    Neuroprotection Research Laboratory, MGH East 149 2401, 13th Street, Charlestown, MA 02129, USA
    Stroke 40:S4-7. 2009
    ..This minireview surveys recent data that support this basic idea, with examples drawn from experimental models broadly relevant to stroke and neurodegeneration...
  5. pmc Extension of the thrombolytic time window with minocycline in experimental stroke
    Yoshihiro Murata
    Neuroprotection Res Lab, Charlestown, MA 02129, USA
    Stroke 39:3372-7. 2008
    ..In this study, we ask whether minocycline can prevent tPA-associated cerebral hemorrhage and extend the reperfusion window in an experimental stroke model in rats...
  6. pmc Experimental model of warfarin-associated intracerebral hemorrhage
    Christian Foerch
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Masschusetts 02129, USA
    Stroke 39:3397-404. 2008
    ..This study describes the development of a mouse model of W-ICH in which hematoma growth and outcomes can be correlated with anticoagulation parameters...
  7. ncbi Targeting extracellular matrix proteolysis for hemorrhagic complications of tPA stroke therapy
    Xiaoying Wang
    Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    CNS Neurol Disord Drug Targets 7:235-42. 2008
    ..The data strongly suggest that targeting the extracellular matrix proteolytic imbalance within the neurovascular unit may provide new approaches for improving the safety and efficacy of thrombolytic reperfusion therapy of stroke...
  8. pmc Protecting against cerebrovascular injury: contributions of 12/15-lipoxygenase to edema formation after transient focal ischemia
    Guang Jin
    Massachusetts General Hospital, Neuroprotection Research Laboratory, 149 13th Street, R 2401, Charlestown, MA 02129, USA
    Stroke 39:2538-43. 2008
    ..The current study was designed to investigate 12/15-LOX involvement in vascular injury in the ischemic brain...
  9. pmc Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons
    Shuzhen Guo
    Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
    Proc Natl Acad Sci U S A 105:7582-7. 2008
    ..Targeting these signals of matrix and trophic coupling between endothelium and neurons may provide new therapeutic opportunities for stroke and other CNS disorders...
  10. ncbi Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke
    Elaine Besancon
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    Trends Pharmacol Sci 29:268-75. 2008
    ..Further in vivo validation of these pathways could ultimately lead us to new therapeutic targets for stroke, trauma and neurodegeneration...
  11. ncbi Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators
    Sun Ryung Lee
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Neurosci Lett 417:1-5. 2007
    ..These data suggest that plasminogen activators may trigger selected pro-inflammatory responses at the neurovascular interface. Whether these effects influence thrombolytic stroke therapy warrants further investigation...
  12. ncbi Cell-cell signaling in the neurovascular unit
    Josephine Lok
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, MGH East 149 2401, Charlestown, MA 02129, USA
    Neurochem Res 32:2032-45. 2007
    ....
  13. pmc Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice
    Michael J Whalen
    Neuroscience Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Cereb Blood Flow Metab 28:490-505. 2008
    ..The data suggest that plasmalemma damage is a fundamental marker of cellular injury after CCI; some injured cells might have an extended window for potential rescue by neuroprotective strategies...
  14. pmc Experimental models, neurovascular mechanisms and translational issues in stroke research
    E H Lo
    Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Charlestown, MA, USA
    Br J Pharmacol 153:S396-405. 2008
    ..Ultimately, both bench-to-bedside and bedside-back-to-bench interactions may be required to overcome the translational hurdles for this challenging disease...
  15. ncbi Effect of neuregulin-1 on histopathological and functional outcome after controlled cortical impact in mice
    Josephine Lok
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
    J Neurotrauma 24:1817-22. 2007
    ..Further studies are therefore warranted to more carefully explore molecular mechanisms, dose-responses, and relationships between morphological outcome and long-term recovery...
  16. pmc Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia
    Young R Kim
    Athinoula Martinos Center for Biomedical Imaging Massachusetts General Hospital, 149 13th Street, Room 2301, Charlestown, MA 02129, USA
    Stroke 39:439-47. 2008
    ..We further investigated neurohemodynamic aspects of the treatment-associated recovery by assessing the therapeutic efficacy of delayed chronic lithium treatment using functional MRI...
  17. pmc Oligovascular signaling in white matter stroke
    Ken Arai
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Biol Pharm Bull 32:1639-44. 2009
    ..A deeper understanding of the mechanisms of oligovascular signaling in normal and pathologic conditions may lead us to new therapeutic targets for stroke and other neurodegenerative diseases...
  18. pmc Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro
    Brian J Lee
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Brain Res 1307:22-7. 2010
    ..Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke...
  19. pmc Increased nuclear apoptosis-inducing factor after transient focal ischemia: a 12/15-lipoxygenase-dependent organelle damage pathway
    Stefanie Pallast
    Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 30:1157-67. 2010
    ..0%+/-2.7%), suggesting cell death through organelle damage. Taken together, these findings show that 12/15-LOX and AIF are sequential actors in a common cell death pathway that may contribute to stroke-induced brain damage...
  20. pmc Annexin A2 combined with low-dose tPA improves thrombolytic therapy in a rat model of focal embolic stroke
    Haihao Zhu
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 30:1137-46. 2010
    ..As a result, brain hemorrhage and infarction are reduced, and the time window for stroke reperfusion prolonged. Our present findings provide a promising new approach for enhancing tPA-based thrombolytic stroke therapy...
  21. pmc Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes
    Kazuhide Hayakawa
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
    Glia 58:1007-15. 2010
    ..These data suggest a novel pathway by which inflammatory cytokines may enhance the ability of reactive astrocytes to release prorecovery mediators after stroke...
  22. pmc Induction of vascular endothelial growth factor and matrix metalloproteinase-9 via CD47 signaling in neurovascular cells
    Changhong Xing
    Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MGH East, 149 2401, 13th St, Charlestown, MA 02129, USA
    Neurochem Res 35:1092-7. 2010
    ..No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke...
  23. pmc Intracranial hemorrhage: mechanisms of secondary brain injury
    Josephine Lok
    Neuroprotection Research Laboratory, Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
    Acta Neurochir Suppl 111:63-9. 2011
    ..This review will highlight some of the cellular pathways in ICH with an emphasis on the mechanisms of secondary injury due to heme toxicity and to events in the coagulation process that are common to both sICH and tICH...
  24. pmc γ-glutamylcysteine ethyl ester protects cerebral endothelial cells during injury and decreases blood-brain barrier permeability after experimental brain trauma
    Josephine Lok
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Neurochem 118:248-55. 2011
    ..These data suggest that the beneficial effects of GCEE on brain endothelial cells and microvessels may contribute to its potential efficacy as a neuroprotective agent in traumatic brain injury...
  25. pmc Annexin A2: a tissue plasminogen activator amplifier for thrombolytic stroke therapy
    Xiang Fan
    Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Stroke 41:S54-8. 2010
    ..Our pilot study using a focal embolic stroke model in rats supports this hypothesis...
  26. pmc Fingolimod provides long-term protection in rodent models of cerebral ischemia
    Ying Wei
    Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
    Ann Neurol 69:119-29. 2011
    ....
  27. pmc 12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress
    Stefanie Pallast
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    J Neurochem 111:882-9. 2009
    ..These findings position 12/15-LOX as the central executioner in an oxidative stress-related neuronal death program...
  28. pmc Brain angiogenesis in developmental and pathological processes: neurovascular injury and angiogenic recovery after stroke
    Ken Arai
    Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    FEBS J 276:4644-52. 2009
    ..Understanding how neurovascular signals and substrates make the transition from initial injury to angiogenic recovery will be important if we are to find new therapeutic approaches for stroke...
  29. pmc Effects of neuroglobin overexpression on mitochondrial function and oxidative stress following hypoxia/reoxygenation in cultured neurons
    Jianxiang Liu
    Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci Res 87:164-70. 2009
    ..Taken together, these data suggest that Ngb is neuroprotective against hypoxia, in part by improving mitochondria function and decreasing oxidative stress...
  30. pmc Neuregulin-1 signaling in brain endothelial cells
    Josephine Lok
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Cereb Blood Flow Metab 29:39-43. 2009
    ..These data suggest that NRG1 signaling is functional and cytoprotective in BMECs...
  31. pmc Lithium upregulates vascular endothelial growth factor in brain endothelial cells and astrocytes
    Shuzhen Guo
    Department of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Stroke 40:652-5. 2009
    ..We tested the hypothesis that lithium can promote the expression of growth factors in brain endothelial cells and astrocytes...
  32. pmc Role of oxidative stress and caspase 3 in CD47-mediated neuronal cell death
    Changhong Xing
    Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MA 02129, USA
    J Neurochem 108:430-6. 2009
    ..We conclude that CD47 mediates neuronal cell death through caspase-dependent and caspase-independent pathways...
  33. pmc CD47 gene knockout protects against transient focal cerebral ischemia in mice
    Guang Jin
    Department of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Massachusetts 02129, USA
    Exp Neurol 217:165-70. 2009
    ..We conclude that CD47 is broadly involved in neuroinflammation, and this integrin-associated-protein plays a role in promoting MMP-9 upregulaton, neutrophil extravasation, brain swelling and progression of acute ischemic brain injury...
  34. pmc Interleukin-1beta augments angiogenic responses of murine endothelial progenitor cells in vitro
    Anna Rosell
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 29:933-43. 2009
    ..Further studies are warranted to assess how interactions between proinflammatory environments and EPC responses may be leveraged to enhance therapeutic angiogenesis...
  35. pmc Neuroprotective roles and mechanisms of neuroglobin
    Zhanyang Yu
    Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Boston, MA, USA
    Neurol Res 31:122-7. 2009
    ..The objectives of this work were to update and summarize recent experimental works on neuroglobin, mainly focus on its neuroprotective effects and the mechanisms...
  36. pmc An oligovascular niche: cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells
    Ken Arai
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    J Neurosci 29:4351-5. 2009
    ..These data suggest that a novel oligovascular niche may be important for sustaining oligodendrocyte renewal and homeostasis in mammalian brain...
  37. pmc Neurovascular effects of CD47 signaling: promotion of cell death, inflammation, and suppression of angiogenesis in brain endothelial cells in vitro
    Changhong Xing
    Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci Res 87:2571-7. 2009
    ..We conclude that CD47 signaling can negatively affect the viability and function of cerebral endothelial cells, further supporting the notion that CD47 may be a potential neurovascular target for stroke and brain injury...
  38. pmc Neuroglobin-overexpression alters hypoxic response gene expression in primary neuron culture following oxygen glucose deprivation
    Z Yu
    Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Program in Neuroscience, Harvard Medical School, 149 13th Street, Room 2411A, Charlestown, MA 02129, USA
    Neuroscience 162:396-403. 2009
    ..Further studies on these gene networks and interactions may lead to better understanding of Ngb in signaling pathways that contribute to neuroprotection...
  39. pmc Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells
    Kazuhide Hayakawa
    Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 31:10666-70. 2011
    ..Our findings demonstrate that VEGF-A can induce OPC migration via an ROS- and FAK-dependent mechanism, and suggest a novel role for VEGF-A in white-matter maintenance and homeostasis...