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(Stroke. 2008;39:2091.)
© 2008 American Heart Association, Inc.

Original Contributions

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

Joseph L. Cheatwood, PhD; April J. Emerick, PhD; Martin E. Schwab, PhD Gwendolyn L. Kartje, MD, PhD

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.

Correspondence to Joseph L. Cheatwood, PhD, Research Service (151), Edward Hines Jr. VA Hospital, 5000 S. 5th Ave, Hines, IL 60141. 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.

Key Words: middle cerebral artery occlusion • interneurons • cerebral cortex • neurons