Axon plasticity in the mammalian central nervous system after injury

Abstract

It is widely recognized that severed axons in the adult central nervous system (CNS) have limited capacity to regenerate. However, mounting evidence from studies of CNS injury response and repair is challenging the prevalent view that the adult mammalian CNS is incapable of structural reorganization to adapt to an altered environment. Animal studies demonstrate the potential to achieve significant anatomical repair and functional recovery following CNS injury by manipulating axon growth regulators alone or in combination with activity-dependent strategies. With a growing understanding in the cellular and molecular mechanisms regulating axon plasticity and the availability of new experimental tools to map detour circuits of functional importance, the future of directing circuit rewiring to achieve functional recovery may be in sight.

A Surviving Intact Branch Stabilizes Remaining Axon Architecture after Injury as Revealed by In Vivo Imaging in the Mouse Spinal Cord

“…Our data support the hypothesis that a surviving intact branch blocks retrograde degeneration of the injured branch from breaching the branch point and also suppresses its regeneration, thus stabilizing the remaining axon architecture. Because collateral sprouting, a form of axonal branching, is widely recognized as an underlying mechanism for some spontaneous recovery after CNS injury (Chen and Zheng, 2014), our finding that an intact axonal branch directly impacts the degenerative and regenerative responses of an injured branch is of heightened significance.…”

A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions

“…Disruption of CSNs and/or CST axons results in motor functional deficits after traumatic injuries like spinal cord injury and stroke. Therefore, a logical therapeutic approach is to promote CST regrowth in a hope to rebuild functional connections (Maier and Schwab, 2006; Ratan and Noble, 2009; Bradke et al, 2012, Tuszynski and Steward, 2012; Chen and Zheng, 2014; Jin and He, 2016; Carmichael et al, 2017). In general, recovery could be achieved either by regenerative growth of injured CST axons across the lesion site, or by compensatory sprouting of spared axons that innervate the denervated areas.…”

“…In general, recovery could be achieved either by regenerative growth of injured CST axons across the lesion site, or by compensatory sprouting of spared axons that innervate the denervated areas. For both types of regrowth, the limited growth ability of adult CSNs is a formidable impediment (Maier and Schwab, 2006; Tuszynski and Steward, 2012; Chen and Zheng, 2014; Jin and He, 2016; Carmichael et al, 2017). …”

Oligodendrocyte involvement in Gulf War Illness

“…Alternatively, neuroinflammation and injury can alter axonal sprouting (Chen & Zheng, ), which would create new axonal branches to be myelinated, thus stimulating synthesis of MBP. To test this hypothesis, we measured the levels of growth associated protein 43 (GAP43), a marker for axonal sprouting (Benowitz & Routtenberg, ) and found that GAP43 levels in subcortical white matter did not change after any treatment condition at 12 hr (Figure S4a, d, 1.0 ± 0.0126 vs. 1.224 ± 0.126 vs. 1.169 ± 0.131 vs. 0.877 ± 0.114 relative GAP43 levels, ANOVA F [3,8] = 2.179, p = 0.1684), 24 hr (Figure S4b, d, 1.0 ± 0.017 vs. 2.249 ± 0.6929 vs. 2.342 ± 0.354 vs. 0.885 ± 0.263 relative GAP43 levels, ANOVA F [3,8] = 3.638, p = 0.0640), or 72 hr (Figure S4c, d, 1.0 ± 0.299 vs. 0.674 ± 0.152 vs. 0.807 ± 0.0355 vs. 0.472 ± 0.123 relative GAP43 levels, ANOVA F [3,8] = 1.534, p = 0.2790) postexposure to DFP and Cort, either alone or in combination.…”