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European Journal of Nuclear Medicine and Molecular Imaging

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01-05-2004 | Molecular Imaging

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

Authors: Carina Mari, Murat Karabiyikoglu, Michael L. Goris, Jonathan F. Tait, Midori Anne Yenari, Francis G. Blankenberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2004

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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Title: Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V
Authors: Carina Mari
Murat Karabiyikoglu
Michael L. Goris
Jonathan F. Tait
Midori Anne Yenari
Francis G. Blankenberg
Publication date: 01-05-2004
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-004-1473-5

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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

Abstract

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Abstract

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