期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 28, 页码 6402-6409出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1492-04.2004
关键词
sensory systems; NT-3; dorsal columns; growth factors; cyclic nucleotides; axon
资金
- NINDS NIH HHS [F31 NS009881, R01 NS09881] Funding Source: Medline
Previous attempts to promote regeneration after spinal cord injury have succeeded in stimulating axonal growth into or around lesion sites but rarely beyond them. We tested whether a combinatorial approach of stimulating the neuronal cell body with cAMP and the injured axon with neurotrophins would propel axonal growth into and beyond sites of spinal cord injury. A preconditioning stimulus to sensory neuronal cell bodies was delivered by injecting cAMP into the L4 dorsal root ganglion, and a postinjury stimulus to the injured axon was administered by injecting neurotrophin-3 (NT-3) within and beyond a cervical spinal cord lesion site grafted with autologous bone marrow stromal cells. One to 3 months later, long-projecting dorsal-column sensory axons regenerated into and beyond the lesion. Regeneration beyond the lesion did not occur after treatment with cAMP or NT-3 alone. Thus, clear axonal regeneration beyond spinal cord injury sites can be achieved by combinatorial approaches that stimulate both the neuronal soma and the axon, representing a major advance in strategies to enhance spinal cord repair.
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