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The Relationship Between Serial [18 F]PBR06 PET Imaging of Microglial Activation and Motor Function Following Stroke in Mice

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Abstract

Purpose

Using [18 F]PBR06 positron emission tomography (PET) to characterize the time course of stroke-associated neuroinflammation (SAN) in mice, to evaluate whether brain microglia influences motor function after stroke, and to demonstrate the use of [18 F]PBR06 PET as a therapeutic assessment tool.

Procedures

Stroke was induced by transient middle cerebral artery occlusion (MCAO) in Balb/c mice (control, stroke, and stroke with poststroke minocycline treatment). [18 F]PBR06 PET/CT imaging, rotarod tests, and immunohistochemistry (IHC) were performed 3, 11, and 22 days poststroke induction (PSI).

Results

The stroke group exhibited significantly increased microglial activation, and impaired motor function. Peak microglial activation was 11 days PSI. There was a strong association between microglial activation, motor function, and microglial protein expression on IHC. Minocycline significantly reduced microglial activation and improved motor function by day 22 PSI.

Conclusion

[18 F]PBR06 PET imaging noninvasively characterizes the time course of SAN, and shows increased microglial activation is associated with decreased motor function.

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Acknowledgments

The authors thank Stanford Center for Innovation in In-Vivo Imaging.

Sources of Funding

Sources of funds were Stanford Bio-X Interdisciplinary Initiatives Program (IIP) Award and Cancer Research Award (to BWL), an NCI ICMIC P50 Award (CA114747 to Dr. Sanjiv Sam Gambhir), an AHA Grant (AHA-0835274 N to RG), a CIRM Grant (RC1-0134 to TDP), NRF and the Ministry of Education, Science and Technology, Korea grants (R31-10105 and NRF-2012M3A9C6049796 to GOA), the Li Ka Shing Foundation and the Department of Radiation Oncology, Stanford University.

Conflict of Interest

The authors declare they have no conflicts of interest

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA

    Frederick M. Lartey, Rehan Ali, Marta Vilalta Colomer, Marjan Rafat, Billy W. Loo Jr. & Edward Graves

  2. Stanford Cancer Institute, Stanford, CA, USA

    Billy W. Loo Jr. & Edward Graves

  3. Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA

    Zheng Miao, Natasha Arksey, Bin Shen, Hongguang Liu & Frederick T. Chin

  4. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA

    Sahar Rosenblum, Theo Palmer & Raphael Guzman

  5. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Miguel A. Alejandre-Alcazar

  6. Integrative Biosciences & Biotechnology, Pohang University of Science & Technology, Kyungbuk, South Korea

    G-One Ahn

  7. Center for Systems Biology and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    John W. Chen

  8. Departments of Neurosurgery and Biomedicine, University of Basel, Basel, Switzerland

    Raphael Guzman

Authors
  1. Frederick M. Lartey
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  2. G-One Ahn
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  3. Rehan Ali
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  4. Sahar Rosenblum
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  5. Zheng Miao
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  6. Natasha Arksey
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  7. Bin Shen
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  8. Marta Vilalta Colomer
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  9. Marjan Rafat
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  10. Hongguang Liu
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  11. Miguel A. Alejandre-Alcazar
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  12. John W. Chen
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  13. Theo Palmer
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  14. Frederick T. Chin
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  15. Raphael Guzman
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  16. Billy W. Loo Jr.
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  17. Edward Graves
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Corresponding authors

Correspondence to Billy W. Loo Jr. or Edward Graves.

Additional information

Frederick M. Lartey and G-One Ahn are co-first authors.

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Lartey, F.M., Ahn, GO., Ali, R. et al. The Relationship Between Serial [18 F]PBR06 PET Imaging of Microglial Activation and Motor Function Following Stroke in Mice. Mol Imaging Biol 16, 821–829 (2014). https://doi.org/10.1007/s11307-014-0745-0

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  • DOI: https://doi.org/10.1007/s11307-014-0745-0

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