A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury

• Published in: The Journal of neuroscience 2013-03, Vol.33 (13), p.5655-5667
• Main Authors: Deng, Ling-Xiao, Deng, Ping, Ruan, Yiwen, Xu, Zao Cheng, Liu, Nai-Kui, Wen, Xuejun, Smith, George M, Xu, Xiao-Ming
• Format: Article
• Language: English
• Subjects: Animals; Biotin - analogs & derivatives; Cell Count; Dextrans; Disease Models, Animal; Electric Stimulation; Evoked Potentials - physiology; Female; Functional Laterality - physiology; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Guided Tissue Regeneration, Periodontal; In Vitro Techniques; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - metabolism; Motor Activity - physiology; Myelin P0 Protein - metabolism; Nerve Regeneration - physiology; Neural Pathways - metabolism; Neural Pathways - pathology; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Schwann Cells - physiology; Schwann Cells - transplantation; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - surgery; Stilbamidines; Synaptophysin - metabolism; Time Factors; Transduction, Genetic - methods
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.2973-12.2013

Descending propriospinal neurons (DPSN) are known to establish functional relays for supraspinal signals, and they display a greater growth response after injury than do the long projecting axons. However, their regenerative response is still deficient due to their failure to depart from growth supportive cellular transplants back into the host spinal cord, which contains numerous impediments to axon growth. Here we report the construction of a continuous growth-promoting pathway in adult rats, formed by grafted Schwann cells overexpressing glial cell line-derived neurotrophic factor (GDNF). We demonstrate that such a growth-promoting pathway, extending from the axonal cut ends to the site of innervation in the distal spinal cord, promoted regeneration of DPSN axons through and beyond the lesion gap of a spinal cord hemisection. Within the distal host spinal cord, regenerated DPSN axons formed synapses with host neurons leading to the restoration of action potentials and partial recovery of function.