title: A re-assessment of the effects of treatment with a non-steroidal anti-inflammatory (ibuprofen) on promoting axon regeneration via RhoA inhibition after spinal cord injury.
abstract: This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat key parts of a study reporting that rats treated with ibuprofen via subcutaneous minipump exhibited greater recovery of motor function and enhanced axonal growth after spinal cord injury. We carried out 3 separate experiments in which young adult female Sprague-Dawley rats received dorsal over-hemisections at T6-T7, and then were implanted with osmotic minipumps for subcutaneous delivery of ibuprofen or saline. Motor function was assessed with the BBB Locomotor Rating Scale, footprint analysis, and with a grid walk task. Combined group sizes for functional analyses were n=34 rats treated with ibuprofen and n=39 controls. Bladder function was assessed by measuring the amount of urine retained in the bladder twice per day. Four weeks post-injury, CST axons were traced by injecting BDA into the sensorimotor cortex; 5HT axons were assessed by immunostaining. Analysis of data from all rats revealed no significant differences between groups. Analysis of data excluding rats with lesions that were larger than intended indicated improved locomotor function in ibuprofen-treated rats at early post-lesion intervals in one of the individual experiments. Rats that received Ibuprofen did not demonstrate statistically significant improvements in bladder function. Quantitative analyses of CST and 5HT axon distribution also did not reveal differences between ibuprofen-treated and control rats. Taken together, our results only partially replicate the findings that treatment with ibuprofen improves motor function after SCI but fail to replicate findings regarding enhanced axon growth.
authors.affiliation: Reeve-Irvine Research Center, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA.
authors.forename: Kelli G
authors.initials: KG
authors.lastname: Sharp
authors.forename: Kelly Matsudaira
authors.initials: KM
authors.lastname: Yee
authors.forename: Travis L
authors.initials: TL
authors.lastname: Stiles
authors.forename: Robert M
authors.initials: RM
authors.lastname: Aguilar
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D059326:Serotonergic Neurons / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012701:Serotonin; D020742:rhoA GTP-Binding Protein; D007052:Ibuprofen
keywords: 5HT; Axon regeneration; Axonal growth; BBB scale; CHPG; CST; Chondroitin sulfate proteoglycans; Corticospinal tract; Ibuprofen; Motor system; Myelin; NSAID; Nonsteroidal anti-inflammatory; Recovery of function; RhoA; Serotonin; Spinal cord injury; Sprouting