Two-tiered inhibition of axon regeneration at the dorsal root entry zone

被引:72
作者
Ramer, MS
Duraisingam, I
Priestley, JV
McMahon, SB
机构
[1] Guys Kings & St Thomas Sch Biomed Sci, Neurosci Res Ctr, Sensory Funct Grp, London SE1 1UL, England
[2] Univ London Queen Mary & Westfield Coll, Royal London Sch Med & Dent, London E1 4NS, England
基金
英国惠康基金;
关键词
neurotrophin-3; regeneration; degeneration; astrocytes; oligodendrocytes; myelin; dorsal root ganglion;
D O I
10.1523/JNEUROSCI.21-08-02651.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glial-derived inhibitory molecules and a weak cell-body response prevent sensory axon regeneration into the spinal cord after dorsal root injury. Neurotrophic factors, particularly neurotrophin-3 (NT-3), may increase the regenerative capacity of sensory neurons after dorsal rhizotomy, allowing regeneration across the dorsal root entry zone (DREZ). Intrathecal NT-3, delivered at the time of injury, promoted an upregulation of the growth-associated protein GAP-43 primarily in large-diameter sensory profiles (which did not occur after rhizotomy alone), as well as regeneration of cholera toxin B-labeled sensory axone across the DREZ and deep into the dorsal horn. However, delaying treatment for 1 week compromised regeneration: although axons still penetrated the DREZ, growth within white matter was qualitatively and quantitatively restricted. This was not associated with an impaired cell-body response (GAP-43 upregulation was equivalent for both immediate and delayed treatments), or with astrogliosis at the DREZ, which begins almost immediately after rhizotomy, but with the delayed appearance of mature EDI-expressing phagocytes in the dorsal white matter between 1 and 2 weeks after lesion, marking the beginning of myelin breakdown. After rhizotomy with immediate NT-3 treatment, regeneration continues beyond 2 weeks, but in the dorsal gray matter rather than in the degenerating dorsal columns. The ability of NT-3 to promote regeneration across the DREZ, but not after the beginning of degeneration after delayed treatment reveals a hierarchy of inhibitory influences: the astrogliotic, but not the degenerative barrier is surmountable by NT-3 treatment.
引用
收藏
页码:2651 / 2660
页数:10
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