on May 8, 2008
Published online before print May 8, 2008, doi: 10.1161/STROKEAHA.107.507426
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Submitted on October 16, 2007
From the Research Service (J.L.C., A.J.E., G.L.K.), Hines VA Hospital, Hines, Ill, USA; the Department of Neurology (J.L.C., G.L.K.), Loyola University Medical Center, Maywood, Ill, USA; the Neuroscience Institute (J.L.C., A.J.E., G.L.K.), Loyola University Medical Center, Maywood, Ill, USA; the Brain Research Institute (M.E.S.), University of Zurich, Switzerland; the Department of Biology (M.E.S.), Swiss Federal Institute of Technology, Zurich, Switzerland; the Neurology Service (G.L.K.), Hines VA Hospital, Hines, Ill, USA; and the Department of Cell Biology, Neurobiology, and Anatomy (G.L.K.), Loyola University Medical Center, Maywood, Ill, USA. * To whom correspondence should be addressed. E-mail: jcheatwood{at}lumc.edu.
Background and Purpose—The Nogo-A protein is an important inhibitor of axonal remodeling after central nervous system injuries, including ischemic stroke. Interfering with the function of Nogo-A via infusion of a therapeutic anti–Nogo-A antibody after stroke increases neuronal remodeling and enhances functional recovery in rats. In this study, we describe the regional distribution of cortical neurons expressing Nogo-A in normal rats and following middle cerebral artery occlusion (MCAO). Methods—Normal and post-MCAO neuronal Nogo-A expression were described via immunohistochemical analyses. All brains were processed for Nogo-A and parvalbumin expression. The level of Nogo-A expression was scored for each cortical area or white matter structure of interest. The number and fluorescent intensity of layer V neurons in contralesional sensorimotor forelimb cortex were also assessed at each time point. Results—Nogo-A expression was observed in both cortical pyramidal neurons and parvalbumin-positive interneurons. Neuronal expression of Nogo-A changed over time in ipsilesional and contralesional cortical areas after MCAO, becoming globally elevated at 28 days after stroke. Nogo-A expression was not observed to fluctuate greatly in the white matter after stroke, with the exception of a transient increase in Nogo-A expression in the external capsule near the stroke lesion. Conclusions—Neuronal Nogo-A expression is significantly increased at 28 days post-MCAO in all examined brain regions. Because of their robust expression of Nogo-A after stroke lesion, both excitatory and inhibitory neurons represent potential targets for anti–Nogo-A therapies in the poststroke cerebral cortex.
Revised on November 14, 2007
Accepted on November 23, 2007
Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat
Joseph L. Cheatwood PhD*;
Key words: middle cerebral artery occlusion • interneurons • cerebral cortex • neurons