Neuroscience 2005 Abstract
| Presentation Number: | 836.4 |
|---|---|
| Abstract Title: | Antibody-induced neutralization of the glial scar promotes sensory axon regeneration. |
| Authors: |
Tan, A. M.*1
; Colletti, M.1
; Levine, J. M.1
1Dept. Neurobiology & Behavior, Univ. of Stony Brook SUNYSB, Stony Brook, NY |
| Primary Theme and Topics |
Development - Transplantation and Regeneration -- Regeneration: CNS |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Trauma<br />-- Spinal cord: Cellular and molecular mechanisms |
| Session: |
836. Regeneration: CNS IV Poster |
| Presentation Time: | Wednesday, November 16, 2005 11:00 AM-12:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # D57 |
| Keywords: | NG2, CSPG, Myelin , Spinal Cord Injury |
Damaged neurons in the adult CNS do not regenerate, in part due to the barrier of the glial scar. The NG2 CSPG is a potent inhibitor of axon growth that is found at high levels in glial scars. To address the function of NG2, we infused anti-NG2 monoclonal antibodies into a bilateral dorsal spinal cord lesion in adult rats. Ascending mechanosensory axons of the sciatic nerve were labeled with the retrograde tracer cholera toxin-B (CTB). At 1-week post-injury, labeled axons in control animals terminated caudal to the lesion in an area of dense NG2 immunoreactivity. Many of these axons had dystrophic endings. In animals treated with neutralizing anti-NG2 antibodies, labeled axons penetrated the caudal border of the lesion and grew beyond the lesion center. Thus, neutralizing NG2 in vivo promotes axon regeneration into the normally growth-inhibitory glial scar.
To increase the growth capacity of DRG neurons, we performed peripheral nerve conditioning-lesions 1 week prior to dorsal column injury. Sensory axon regeneration was examined 4 weeks later. After treatment with control, non-neutralizing antibodies, axons grew into the lesion cavity but turned dorsally, exiting the spinal cord, and growing preferentially along the dorsal surface of the cord and into pieces of remaining dorsal roots. In contrast, when treated with neutralizing anti-NG2 antibodies, lesion-primed sensory axons grew into and beyond the lesion cavity for distances as long as 6mm. These axons were not surgically spared since no labeled profiles were observed in the gracile nucleus. Neurolucida-based reconstructions of axon trajectories from sagital sections showed that 43.6„b16.9% of all the labeled axons were found within the white matter rostral to the injury. These results suggest that although a peripheral nerve conditioning lesion enhances growth, it does not desensitize neurons to NG2-mediated inhibition/repulsion. The combinatorial approach used here results in topographically correct axon regeneration, a prerequisite for functional recovery.
To increase the growth capacity of DRG neurons, we performed peripheral nerve conditioning-lesions 1 week prior to dorsal column injury. Sensory axon regeneration was examined 4 weeks later. After treatment with control, non-neutralizing antibodies, axons grew into the lesion cavity but turned dorsally, exiting the spinal cord, and growing preferentially along the dorsal surface of the cord and into pieces of remaining dorsal roots. In contrast, when treated with neutralizing anti-NG2 antibodies, lesion-primed sensory axons grew into and beyond the lesion cavity for distances as long as 6mm. These axons were not surgically spared since no labeled profiles were observed in the gracile nucleus. Neurolucida-based reconstructions of axon trajectories from sagital sections showed that 43.6„b16.9% of all the labeled axons were found within the white matter rostral to the injury. These results suggest that although a peripheral nerve conditioning lesion enhances growth, it does not desensitize neurons to NG2-mediated inhibition/repulsion. The combinatorial approach used here results in topographically correct axon regeneration, a prerequisite for functional recovery.
Supported by NYSCIRB, CRPF and NIH
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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