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

Abstract

The GTP-binding protein RhoA regulates microfilament dynamics in many cell types and mediates the inhibition of axonal regeneration by myelin and chondroitin sulfate proteoglycans. Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al., 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al., 2007). Here, we confirm that ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro. Following 4 weeks of subcutaneous administration of ibuprofen, beginning 3 days after spinal cord contusion, animals recovered walking function to a greater degree, with twice as many rats achieving a hind limb weight-bearing status. We examined the relative role of tissue sparing, axonal sprouting, and axonal regeneration in the action of ibuprofen. Histologically, ibuprofen-treated animals display an increase in spared tissue without an alteration in astrocytic or microglial reaction. Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal fibers in the injured spinal cord, but does not permit caudal corticospinal regeneration after spinal contusion. Treatment of mice with complete spinal cord transection demonstrates long-distance raphespinal axon regeneration in the presence of ibuprofen. Thus, administration of ibuprofen improves the recovery of rats from a clinically relevant spinal cord trauma by protecting tissue, stimulating axonal sprouting, and allowing a minor degree of raphespinal regeneration.

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

“…Again, in many of these studies, the drug was given either prior to or within minutes of injury. Ibuprofen, however, has more recently been found to promote both histologic and behavioral improvements in thoracic contusion SCI models when administered 3 days post injury (Wang et al, 2009) or even 7 days post injury (Fu et al, 2007). These two studies also revealed that ibuprofen was superior to naproxen in both behavioral and non-behavioral outcomes.…”

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

“…Alexa Fluor 594 horse anti-mouse and Alexa Fluor 488 goat anti-rabbit antibodies (Molecular Probes, Eugene, OR) were used as secondary antibodies. Quantification of GFAP expression was performed through intensity analysis using Adobe Photoshop software (San Jose, CA) within rectangular areas of 100 m (width) ϫ dorsoventral diameter of spinal cord (height) extending from 600 m cranial to 600 m caudal from the lesion center (Wang et al, 2009).…”

Anti-edema effect of melatonin on spinal cord injury in rats

“…Aquaporin-4 (AQP4) protein is highly expressed in the central nervous system (CNS) (ref. 19,20 ), the expression changes of which are associated with spinal cord edema and the permeability of bloodspinal cord barrier 21,22 . The expression of AQP4 in injured spinal cords changes in a similar manner to the water content of spinal cord 23,24 .…”