(Stroke. 2000;31:2692.)
© 2000 American Heart Association, Inc.
Original Contributions |
99mTc Annexin V Imaging of Neonatal Hypoxic Brain Injury
From the Department of Radiology (H.D., A.d.C., W.H.S., T.E., A.K., M.M., F.G.B.), Stanford University School of Medicine, Stanford, Calif; the Department of Pediatrics (W.R.), Lucile Salter Packard Children’s Hospital at Stanford, Palo Alto, Calif; the Department of Laboratory Medicine, (J.F.T.), University of Washington, Seattle; and the Department of Neurology, Neurological Sciences, and Neurosurgery (M.Y.), Stanford Stroke Center, Palo Alto, Calif.
Correspondence to Francis G. Blankenberg, MD, Department of Radiology, Stanford University School of Medicine, 300 Pasture Dr, Stanford, CA 94305-5105. E-mail blankenb{at}leland.stanford.edu
Background and Purpose: —Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII.
Methods—Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (n=17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with 99mTc annexin V. Radionuclide images were recorded 2 hours later.
Results—Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier.
Conclusions—Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.
Editorial Comment
A/CCM Laboratories Johns Hopkins University School of Medicine Baltimore, Maryland
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