AAVshRNA-Mediated Suppression of PTEN in Adult Rats in Combination with Salmon Fibrin Administration Enables Regenerative Growth of Corticospinal Axons and Enhances Recovery of Voluntary Motor Function after Cervical Spinal Cord Injury

The Journal of Neuroscience, 2014 · DOI: 10.1523/JNEUROSCI.1996-14.2014 · Published: July 23, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates whether suppressing a gene called PTEN in adult rats, along with injecting salmon fibrin into a spinal cord injury site, can help regenerate damaged nerve fibers and improve motor function. Rats were trained to perform a reaching task, then received injections to reduce PTEN levels, followed by a spinal cord injury and fibrin treatment. Their motor skills were assessed over 10 weeks. The researchers found that rats with both PTEN suppression and fibrin treatment showed better motor recovery and more nerve fiber regeneration compared to those with only PTEN suppression or neither treatment.

Study Duration

10 weeks (behavioral assessment) + 3 weeks (BDA tracing)

Participants

Adult female Sprague Dawley rats (n=60 initially)

Evidence Level

Not specified

Key Findings

1
AAVshRNA-mediated suppression of PTEN in adult cortical motoneurons enhances regenerative growth of CST axons after SCI.
2
The combination of AAVshRNA-mediated suppression of PTEN with salmon fibrin injection into the injury site was associated with improved forepaw-grasping function.
3
Rats that received AAVshPTEN and salmon fibrin had larger numbers of BDA-labeled axons at the edge of the SCI lesion.

Research Summary

This study examined the effects of PTEN knockdown and salmon fibrin injection on corticospinal tract (CST) regeneration and motor function recovery in adult rats after spinal cord injury (SCI). The combination of AAVshRNA-mediated PTEN suppression and salmon fibrin injection resulted in enhanced regenerative growth of CST axons and improved forepaw motor function recovery compared to either treatment alone. The findings suggest that targeting both intrinsic growth potential (PTEN deletion) and extrinsic factors at the injury site (salmon fibrin) can significantly improve voluntary motor function after SCI.

Practical Implications

Combination Therapy Potential

Combining PTEN suppression with biomaterial interventions like salmon fibrin may be a promising strategy for promoting axon regeneration and functional recovery after SCI.

Adult Neuron Regeneration

This study demonstrates that regenerative growth can be induced in adult neurons through genetic manipulation combined with a supportive lesion environment.

Translation to Humans

The use of rats, which develop SCI-related cavities similar to humans, suggests that these findings may be more translatable to human SCI treatment strategies.

Study Limitations

1
More tract tracing failures than we typically obtain (rats with no or minimal CST labeling), reducing the number available for anatomical analysis.
2
Labeled axons were not as strongly labeled as is typical in our studies, probably because BDA staining was done using slide-mounted rather than free-floating sections.
3
The enhanced recovery begins quite early post-lesion (by 3 weeks after SCI), which is unlikely to be related to long-distance axon regeneration, but could reflect local, short-distance growth.

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