Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

JOURNAL OF NEUROTRAUMA, 2009 · DOI: 10.1089=neu.2007.0464 · Published: January 1, 2009

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The study investigates how ibuprofen, a common anti-inflammatory drug, can aid recovery after spinal cord injury. It focuses on ibuprofen's ability to reduce RhoA activity, a protein that inhibits axonal regeneration. Researchers found that ibuprofen reduces RhoA signaling and myelin-induced inhibition of neurite outgrowth in lab experiments. Furthermore, rats treated with ibuprofen after spinal cord injury showed improved walking ability. The benefits of ibuprofen appear to stem from protecting spinal cord tissue, stimulating the growth of new nerve connections, and enabling some nerve regeneration. This suggests ibuprofen has potential as a therapy for spinal cord injuries.

Study Duration

4 weeks

Participants

Female Sprague-Dawley rats (11–12 weeks of age, 250–270 g) and Female C57=Bl6 mice (8–9 weeks of age, 20 g body weight)

Evidence Level

Not specified

Key Findings

1
Ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro.
2
Ibuprofen-treated animals display an increase in spared tissue without an alteration in astrocytic or microglial reaction.
3
Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal ﬁbers in the injured spinal cord.

Research Summary

This study demonstrates that ibuprofen promotes recovery from spinal cord contusion through a complex mechanism including axonal sprouting, neuroprotection, and raphespinal regeneration. Ibuprofen treatment suppresses Rho activity and rats recover a greater degree of neurological function if treated with ibuprofen which correlates with neuroprotection and with CST and raphespinal axon growth. The complete transection work proves that ibuprofen actually stimulates axonal regeneration. The study also showed that spinal cord tissue is spared by the ibuprofen treatment after contusion, demonstrating a combined protective and regenerative mechanism.

Practical Implications

Therapeutic Potential for SCI

Ibuprofen and related Rho-inhibiting compounds have therapeutic potential for spinal cord injury.

Subacute Therapy

Ibuprofen administration may only be necessary in the subacute period, further avoiding the risks of chronic administration.

Screening for Optimal Rho Inhibition

Compounds related to ibuprofen might provide a useful starting point to screen for optimal Rho pathway inhibition and future SCI or stroke recovery therapeutics.

Study Limitations

1
Ibuprofen-dependent axonal regeneration is conﬁned to a small subset of raphespinal ﬁbers after complete transection.
2
No BDA-labeled CST ﬁbers were observed caudal to the lesion sites in any rats.
3
The study had a 3-day delay in systemic ibuprofen treatment of contusion.

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