Nogo-A expression after focal ischemic stroke in the adult rat.
OBJECTIVE
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.
Cheatwood
Joseph L
JL
Research Service (151), Edward Hines Jr. VA Hospital, 5000 S. 5th Ave, Hines, IL 60141, USA. jcheatwood@lumc.edu
Emerick
April J
AJ
Schwab
Martin E
ME
Kartje
Gwendolyn L
GL
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D003337:Corpus Callosum / Q000378:metabolism; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008953:Models, Anatomic; D008954:Models, Biological; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat