Exogenous BDNF enhances the integration of chronically injured axons that regenerate through a peripheral nerve grafted into a chondroitinase-treated spinal cord injury site

Exp Neurol, 2013 · DOI: 10.1016/j.expneurol.2012.09.011 · Published: January 1, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This research explores how to improve the regrowth of damaged nerve fibers in spinal cord injuries. The scientists used peripheral nerve grafts (PNG) to provide a path for the nerves to regrow. They also used an enzyme called chondroitinase (ChABC) to help the nerves cross scar tissue. The study tested whether adding a growth factor called BDNF would further improve nerve regrowth and function. The results showed that while ChABC helps nerves regrow across the scar, adding BDNF didn't increase the number of regrown nerves, but it did improve their ability to connect and function with other nerve cells.

Study Duration

8 weeks

Participants

Adult female Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
ChABC treatment alone promoted axonal regeneration beyond the graft-host interface.
2
Combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord.
3
Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated.

Research Summary

The study investigated whether exogenous BDNF could enhance axonal regeneration beyond a ChABC-treated glial interface in a chronic spinal cord injury model using peripheral nerve grafts (PNGs). While ChABC treatment promoted axonal regeneration, the addition of BDNF did not further increase the number of axons regenerating into the spinal cord. However, BDNF overexpression, in combination with ChABC, enhanced the functional integration of regenerated axons, as indicated by increased c-Fos expression in spinal cord neurons upon electrical stimulation of the PNG.

Practical Implications

Therapeutic Potential

BDNF can be used to enhance the effects of even a small number of regenerated fibers.

Combination Therapy

Combining BDNF with other treatments, such as ChABC, may be a beneficial strategy for promoting functional recovery after SCI.

Synaptic Plasticity

BDNF's ability to potentiate synapse formation or synaptic transmission indicates that it can be used to enhance the effects of even a small number of regenerated fibers.

Study Limitations

1
The study used an incomplete SCI model, which may have limited the observation of functional improvements.
2
The lack of correlation between increased c-Fos induction and behavioral changes suggests that regenerated axons may have formed synapses on inappropriate target neurons.
3
The treadmill speed was kept constant for all animals which precluded seeing functional improvements.

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