RhoA-inhibiting NSAIDs promote axonal myelination after spinal cord injury.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used to relieve pain and inflammation in humans via cyclooxygenase inhibition. Our recent research suggests that certain NSAIDs including ibuprofen suppress intracellular RhoA signal and improve significant axonal growth and functional recovery following axonal injury in the CNS. Several NSAIDs have been shown to reduce generation of amyloid-beta42 peptide via inactivation of RhoA signal, supporting potent RhoA-repressing function of selected NSAIDs. In this report, we demonstrate that RhoA-inhibiting NSAIDs ibuprofen and indomethacin dramatically reduce cell death of oligodendrocytes in cultures or along the white matter tracts in rats with a spinal cord injury. More importantly, we demonstrate that treatments with the RhoA-inhibiting NSAIDs significantly increase axonal myelination along the white matter tracts following a traumatic contusion spinal cord injury. In contrast, non-RhoA-inhibiting NSAID naproxen does not have such an effect. Thus, our results suggest that RhoA inactivation with certain NSAIDs benefits recovery of injured CNS axons not only by promoting axonal elongation, but by enhancing glial survival and axonal myelination along the disrupted axonal tracts. This study, together with previous reports, supports that RhoA signal is an important therapeutic target for promoting recovery of injured CNS and that RhoA-inhibiting NSAIDs provide great therapeutic potential for CNS axonal injuries in adult mammals.

• Authors: Bin Xing, Hui Li, Hongyu Wang, Dhriti Mukhopadhyay, Daniel Fisher, Christopher J Gilpin, Shuxin Li
• Journal: Experimental neurology (Exp Neurol) Vol. 231 Issue 2 Pg. 247-60 (Oct 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21781963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• rhoA GTP-Binding Protein
• Ibuprofen
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Axons (drug effects, metabolism)
• Cells, Cultured
• Female
• Ibuprofen (pharmacology, therapeutic use)
• Indomethacin (pharmacology, therapeutic use)
• Myelin Sheath (drug effects, metabolism)
• Nerve Fibers, Myelinated (drug effects, metabolism)
• Nerve Regeneration (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Spinal Cord (drug effects, metabolism, physiopathology)
• Spinal Cord Injuries (drug therapy, metabolism, physiopathology)
• rhoA GTP-Binding Protein (antagonists & inhibitors)