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Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V

  • Molecular Imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

In this study we wished to determine whether technetium-99m annexin V, an in vivo marker of cellular injury and death, could be used to noninvasively monitor neuronal injury following focal middle cerebral artery (MCA) occlusion/reperfusion injury. Sixteen adult male Sprague-Dawley rats (along with four controls) underwent left (unilateral) MCA intraluminal beaded thread occlusion for 2 h followed by reperfusion. One hour following tail vein injection of 5–10 mCi of 99mTc-annexin V, animals underwent either single-photon emission computerized tomography (SPECT) or autoradiography followed by immunohistochemical analyses. There was abnormal, bilateral, multifocal uptake of 99mTc-annexin V in each cerebral hemisphere as seen by both SPECT and autoradiography at 4 h and 1, 3, and 7 days after initiation of occlusion. The average maximal annexin V uptake at 4 h was 310%±85% and 365%±151% above control values (P<0.006) within the right and left hemispheres, respectively, peaking on day 3 with values of 925%±734% and 1,194%±643% (P<0.03) that decreased by day 7 to 489%±233% and 785%±225% (P<0.01). Total lesional volume of the left hemisphere was 226%, 261%, and 451% (P<0.03) larger than the right at 4, 24, and 72 h after injury, respectively. Annexin V localized to the cytoplasm of injured neurons ipsilateral to the site of injury as well as to otherwise normal-appearing neurons of the contralateral hemisphere as confirmed by dual fluorescent microscopy. It is concluded that there is abnormal bilateral, multifocal annexin V uptake, greater on the left than on the right side, within 4 h of unilateral left MCA ischemic injury and that the uptake peaks at 3 days and decreases by 7 days after injury. This pattern suggests that neuronal stress may play a role in the response of the brain to focal injury and be responsible for annexin V uptake outside the region of ischemic insult.

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Acknowledgements

This work was supported by The National Institutes of Health, HL-61717, NINDS, R01 NS40516 (MAY). The authors also wish to thank Bonnie Bell for her efforts in preparing histopathologic sections for routine and immunohistochemical analyses.

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Authors and Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, Stanford University Hospital, Stanford, CA 94305, USA

    Carina Mari, Michael L. Goris & Francis G. Blankenberg

  2. Departments of Neurosurgery and Neurology, Stanford University Hospital, Stanford, CA 94305, USA

    Murat Karabiyikoglu & Midori Anne Yenari

  3. Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195-7110, USA

    Jonathan F. Tait

  4. Division of Pediatric Radiology, Department of Radiology, Stanford University, Lucile Salter Packard Children’s Hospital, 725 Welch Road, Room #1673, Palo Alto, CA 94305, USA

    Francis G. Blankenberg

Authors
  1. Carina Mari
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  2. Murat Karabiyikoglu
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  3. Michael L. Goris
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  4. Jonathan F. Tait
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  5. Midori Anne Yenari
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  6. Francis G. Blankenberg
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Corresponding author

Correspondence to Francis G. Blankenberg.

Additional information

Carina Mari and Murat Karabiyikoglu contributed equally to the work presented here.

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Mari, C., Karabiyikoglu, M., Goris, M.L. et al. Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V. Eur J Nucl Med Mol Imaging 31, 733–739 (2004). https://doi.org/10.1007/s00259-004-1473-5

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  • DOI: https://doi.org/10.1007/s00259-004-1473-5

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