Nogo-A is associated with secondary degeneration of substantia nigra in hypertensive rats with focal cortical infarction.

Abstract

We investigated the association of Nogo-A protein, a myelin-associated inhibitor of axon regeneration, with secondary damage of the ipsilateral substantia nigra pars reticulata (SNr) after distal middle cerebral artery occlusion (dMCAO) in adult stroke-prone, renovascular hypertensive rats. Intracerebroventricular infusion of NEP1-40, a Nogo-66 receptor antagonist peptide, or vehicle was administered starting 24h after dMCAO and continued for 1, 2, or 4 weeks. The expression of Nogo-A in the ipsilateral SNr was assessed by immunohistochemistry. Neuron death and apoptosis were evaluated using Nissl and terminal uridine nick-end labeling (TUNEL) staining. Glial activation was monitored by immunoreactivity of glial fibrillary acidic protein and the oligodendrocyte marker RIP. Axonal damage and regeneration were determined by Bielschowsky's silver staining and immunoreactivity of growth associated protein 43 and microtubule associated protein 2. We found progressive damage in the center of the ipsilateral SNr through 4 weeks after dMCAO. The neuronal loss was topographically related to axonal degeneration that occurred indirectly from the infarcted cortex. Nogo-A protein in oligodendrocytes was persistently increased in the damaged SNr. Administration of NEP1-40 inhibited Nogo-A expression, the loss of neurons, apoptosis, and proliferation of oligodendrocytes and astrocytes. It also boosted the regenerative response of injured axons and encouraged compensatory neurite growth in the ipsilateral SNr. Our data suggest that secondary damage in the ipsilateral SNr may be due to trans-synaptic axonal degeneration that followed the cortical infarct. Further, we showed that Nogo-A is involved in axonal degeneration, and NEP1-40 reduces secondary nigral damage after focal cortical ischemia.

• Authors: Fang Wang, Shihui Xing, Meixia He, Qinghua Hou, Shangjie Chen, Xiaohui Zou, Zhong Pei, Jinsheng Zeng
• Journal: Brain research (Brain Res) Vol. 1469 Pg. 153-63 (Aug 21 2012) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 22771857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Glial Fibrillary Acidic Protein
• Myelin Proteins
• Nogo Proteins
• Rtn4 protein, rat

Topics

• Animals
• Astrocytes (metabolism, pathology)
• Axons (metabolism, pathology)
• Cerebral Infarction (complications, metabolism, pathology)
• Glial Fibrillary Acidic Protein (metabolism)
• Hypertension, Renovascular (complications, metabolism, pathology)
• Myelin Proteins (metabolism)
• Nerve Degeneration (etiology, metabolism, pathology)
• Neurons (metabolism, pathology)
• Nogo Proteins
• Oligodendroglia (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Substantia Nigra (metabolism, pathology)