Imatinib Enhances Functional Outcome after Spinal Cord Injury

PLoS ONE, 2012 · DOI: 10.1371/journal.pone.0038760 · Published: June 19, 2012

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This study investigates whether imatinib, a tyrosine kinase inhibitor, can improve functional outcomes in rats with spinal cord injuries. Imatinib was administered orally for five days, starting shortly after the injury. The researchers found that imatinib-treated rats showed enhanced blood-spinal cord-barrier integrity, improved hindlimb locomotor function, better sensorimotor integration, and improved bladder function. Additionally, there was reduced inflammation and increased tissue preservation in the spinal cord. These positive effects suggest that imatinib could be a potential therapeutic candidate for clinical trials in spinal cord injuries. The rapid onset of these effects implies a neuroprotective mechanism rather than a neurorestorative one.

Study Duration

56 Days

Participants

36 rats subjected to contusion spinal cord injury

Evidence Level

Not specified

Key Findings

1
Imatinib significantly enhanced hindlimb locomotor function. By day 56 post-injury, 70% of imatinib-treated rats had regained the ability to make uncoordinated weight-supported steps.
2
Imatinib treatment significantly reduced the areas of CD68 immunoreactive activated macrophages/microglia within the injury site compared to PBS treatment.
3
Imatinib increased immunolabeling of the endothelial tight junction protein, claudin-5, indicating normalization of the blood-spinal cord-barrier.

Research Summary

This study demonstrated that imatinib treatment following spinal cord injury in rats led to significant improvements in functional outcomes, including enhanced locomotor function, sensorimotor integration, and bladder function. The beneficial effects of imatinib were associated with increased tissue preservation, reduced inflammation, attenuated astrogliosis, and decreased deposition of chondroitin sulfate proteoglycans at the injury site. The study also found that imatinib enhanced blood-spinal cord-barrier integrity and reduced the expansion and proliferation of PDGFR expressing cells, suggesting a potential mechanism for its neuroprotective effects.

Practical Implications

Potential Therapeutic Candidate

Imatinib, an already clinically used drug, could be a promising therapeutic candidate for treating spinal cord injuries, potentially accelerating the path to clinical trials.

Neuroprotective Strategy

The neuroprotective effects of imatinib suggest a focus on early intervention strategies to minimize secondary damage following spinal cord injury.

Bladder Function Improvement

The restoration of bladder function with imatinib is particularly significant, given the high priority of bladder function for spinal cord injury patients.

Study Limitations

1
The study was conducted on rats, and the results may not directly translate to humans.
2
The exact mechanisms of action of imatinib in spinal cord injury require further investigation.
3
Long-term effects of imatinib treatment were not assessed beyond the 56-day study period.

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