Enhanced regenerative axon growth of multiple fibre populations in traumatic spinal cord injury following scar-suppressing treatment

Abstract

We analysed the effect of scar-suppressing treatment (anti-scarring treatment; AST) on augmenting axonal regeneration of various neuronal populations following spinal cord injury (SCI) in adult rat. AST included local iron chelator (2,2'-dipyridine-5,5'-dicarboxylic acid) injection and 8-bromo-cyclic adenosine monophosphate application to the lesion core. In previous studies, this treatment promoted long-distance regeneration of cut corticospinal tract axons, neuroprotection of projecting cortical neurons and functional improvement of treated rats [N. Klapka et al. (2005)Eur. J. Neurosci., 22, 3047-3058]. Treatment yielded significantly enhanced regrowth of descending serotonergic (5-HT), catecholaminergic (tyrosine hydroxylase; TH), corticospinal and rubrospinal axons into the lesion zone, as assessed by anterograde tracing and immunohistochemistry followed by quantification of axon profiles at 5 and 12 weeks post-injury. In addition, the determination of axons crossing the proximal borderline from uninjured tissue into fibrous scar area revealed a significant AST-promoted increase of intersecting fibres for 5-HT, TH and calcitonin gene-related peptide containing ascending sensory fibres. For a prolonged time period after lesion, the delayed (secondary) scar developing in treated rats is significantly more permeable for all analysed axon tracts than the initial (primary) scar forming in injured control animals lacking treatment. Furthermore, enhanced outgrowth of descending axons from fibrous scar into distal healthy spinal tissue was achieved in treated animals, and is in line with previous functional studies [S. Hermanns et al. (2001) Restor. Neurol. Neurosci., 19,139-148; N. Klapka et al. (2005)Eur. J. Neurosci., 22, 3047-3058]. Our findings indicate that AST exerts a prolonged beneficial effect on fibrous scarring allowing enhanced axonal regrowth of different fibre tracts in SCI regardless of their distinct regenerative demands.