The Subventricular Zone Response to Stroke Is Not a Therapeutic Target of Anti-Nogo-A Immunotherapy Journal Article


Authors: Shepherd, D. J.; Tsai, S. Y.; Cappucci, S. P.; Wu, J. Y.; Farrer, R. G.; Kartje, G. L.
Article Title: The Subventricular Zone Response to Stroke Is Not a Therapeutic Target of Anti-Nogo-A Immunotherapy
Abstract: Ischemic stroke is a leading cause of adult disability with no pharmacological treatments to promote the recovery of lost function. Neutralizing antibodies against the neurite outgrowth inhibitor Nogo-A have emerged as a promising treatment for subacute and chronic stroke in animal models; however, whether anti-Nogo-A treatment affects poststroke neurogenesis remains poorly understood. In this study, we confirmed expression of Nogo-A by neuroblasts in the adult rat subventricular zone (SVZ), a major neurogenic niche; however, we found no evidence that Nogo-A was expressed at the surface of these cells. In vitro migration assays demonstrated that Nogo-A signaling induced a modest reduction in neuroblast migration speed, while anti-Nogo-A antibodies had no effect on motility properties. Using a permanent distal middle cerebral artery occlusion model of cortical stroke, we found that the number of proliferating cells in the SVZ was unaffected in response to stroke, while neuroblast mobilization from the SVZ toward the stroke lesion correlated positively with lesion size. However, we found no evidence that proliferation or neuroblast mobilization were affected by anti-Nogo-A antibody treatment. Our results suggest that the SVZ is not a therapeutic target of anti-Nogo-A immunotherapy, and contribute to our understanding of the SVZ response to cortical stroke.
Journal Title: Journal of neuropathology and experimental neurology
Volume: 76
Issue: 8
ISSN: 1554-6578; 0022-3069
Publisher: American Association of Neuropathologists, Inc. This work is written by US Government employees and is in the public domain in the US  
Journal Place: England
Date Published: 2017
Start Page: 683
End Page: 696
Language: eng
DOI/URL:
Notes: LR: 20170822; CI: 2017; JID: 2985192R; 0 (Antibodies); 0 (Nerve Tissue Proteins); 0 (Nogo Proteins); 0 (Nogo Receptor 1); 0 (Receptors, Lysosphingolipid); 0 (Rtn4r protein, rat); 0 (sphingosine-1-phosphate receptor-2, rat); 83HN0GTJ6D (Cyclosporine); G34N38R2N1 (Bromodeoxyuridine); OTO: NOTNLM; 2017/08/10 06:00 [entrez]; 2017/08/10 06:00 [pubmed]; 2017/08/23 06:00 [medline]; ppublish