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

作者：Sharp Kelli G; Yee Kelly Matsudaira; Stiles Travis L; Aguilar Robert M; Steward Oswald^*

来源：Experimental Neurology, 2013, 248: 321-337.

DOI：10.1016/j.expneurol.2013.06.023

• Spinal cord injury
• BBB scale
• RhoA
• Nonsteroidal anti-inflammatory
• NSAID
• Ibuprofen
• Axonal growth
• Axon regeneration
• Myelin
• 5HT
• Serotonin
• Corticospinal tract
• CST
• Sprouting
• Chondroitin sulfate proteoglycans
• CHPG
• Motor system
• Recovery of function

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 carded 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.

• 出版日期2013-10