Chondroitinase ABC Enhances Pericontusion Axonal Sprouting But Does Not Confer Robust Improvements in Behavioral Recovery

JOURNAL OF NEUROTRAUMA, 2010 · DOI: 10.1089/neu.2010.1470 · Published: November 1, 2010

Neurology Neuroplasticity Rehabilitation

Simple Explanation

Traumatic brain injury (TBI) often leads to lasting functional impairments. Promoting plasticity in the injured brain might help improve functional outcomes. The study aimed to see if infusing chondroitinase ABC, an enzyme, into the contusion site would enhance axon sprouting and improve forelimb function after TBI. While chondroitinase increased axon sprouting, it did not significantly improve overall forelimb function, although there was some improvement in unskilled limb use.

Study Duration

28 days

Participants

Adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Acute chondroitinase infusion decreased intact CSPGs and significantly increased pericontusional cortical grey and white matter GAP43-positive axon sprouting at 7 days post-injury.
2
A return of intact CSPGs at later time points likely contributed to the absence of persistently increased levels of axon sprouting by 14–21 days post-injury.
3
There was a chondroitinase-induced improvement in recovery from unskilled limb use deﬁcits on the staircase forelimb reaching test toward sham-injured values at 28 days.

Research Summary

This study investigates whether chondroitinase ABC infusion enhances axon sprouting and improves behavioral deficits after traumatic brain injury (TBI) in rats. Chondroitinase treatment increased axon sprouting in the pericontusional area at 7 days post-injury, but this effect was not sustained at later time points due to the return of CSPGs. While overall forelimb function was not significantly improved, chondroitinase treatment did lead to a minor improvement in unskilled limb use on the staircase test at 28 days post-injury.

Practical Implications

Combinatorial Therapies

Combining chondroitinase with neurotrophins and rehabilitation may lead to more robust axon sprouting and improved behavioral outcomes.

Timing of Intervention

Acute intervention with chondroitinase appears more optimal for axonal sprouting than delayed intervention.

Targeted Delivery

Further research is needed to determine if delayed chondroitinase intervention or interventions in other brain regions would promote greater plasticity and functional outcome.

Study Limitations

1
The increase in axon sprouting was not prolonged beyond the period of chondroitinase infusion.
2
No significant functional benefits in skilled limb use were observed due to chondroitinase intervention.
3
Tissue atrophy in the contusion core may have contributed to the lack of sustained deficits in CSPGs.

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