Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice

Eur J Neurosci, 2012 · DOI: 10.1111/ejn.12017 · Published: December 1, 2012

Simple Explanation

This study investigates whether degrading chondroitin sulphate proteoglycans (CSPGs) with chondroitinase ABC (ChABC) can promote compensatory sprouting of the intact corticospinal tract (CST) following unilateral injury and restore function to the denervated forelimb in adult mice. Following a unilateral pyramidotomy (injury to one side of the CST), mice treated with ChABC showed a marked recovery of function, with forelimb symmetry fully restored by five weeks post-injury. The functional recovery was associated with robust sprouting of the uninjured CST, with numerous axons crossing the midline in the brainstem and spinal cord.

Study Duration

6 Weeks

Participants

31 adult male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
ChABC treatment enables robust sprouting of intact CST fibers across the midline to innervate denervated grey matter territory in the brainstem and spinal cord.
2
Plasticity of the intact CST was associated with recovery of forepaw symmetry.
3
CSPG degradation can enable compensatory sprouting of the intact CST, leading to restored function in the denervated forepaw.

Research Summary

The study demonstrates that degrading CSPGs promotes midline crossing and reinnervation of denervated target regions by intact CST axons. ChABC treatment resulted in functional recovery of the denervated forepaw in mice following unilateral pyramidotomy, restoring forelimb symmetry. The compensatory sprouting of the intact CST was linked to the functional recovery, indicating that CSPG digestion can enable neural reorganization and restore motor function.

Practical Implications

Therapeutic Potential

Enhancing compensatory sprouting using ChABC provides a route to restore function which could be applied to disorders such as spinal cord injury and stroke.

Plasticity Enhancement

Modifying CSPGs post-injury can lead to compensatory reorganisation of a major descending motor pathway and can restore function to the denervated forelimb.

Combination Therapies

Combining Nogo-A neutralisation with CSPG degradation could synergistically enhance the potential for plasticity.

Study Limitations

1
Single housing of mice may have limited the extent of sprouting compared to group housing.
2
Assessment of CSPG digestion patterns was made at only one post-injury time point.
3
Other uninjured systems may also have contributed to the functional repair.

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