title: 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.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.forename: Stephane
authors.initials: S
authors.lastname: Budel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Baughman
authors.forename: Grahame
authors.initials: G
authors.lastname: Gould
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D019771:Axotomy; D002642:Chick Embryo; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D005260:Female; D020439:Growth Cones / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007052:Ibuprofen / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D041681:NIH 3T3 Cells; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D011903:Raphe Nuclei / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020742:rhoA GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006131:Growth Inhibitors; D020742:rhoA GTP-Binding Protein; D007052:Ibuprofen