Nogo-A expression after focal ischemic stroke in the adult rat

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.