A re-assessment of treatment with a tyrosine kinase inhibitor (imatinib) on tissue sparing and functional recovery after spinal cord injury.
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 imatinib (Gleevec®, Novartis) after spinal cord contusion injury exhibited enhanced bladder function, greater recovery of motor function, and increased tissue sparing. Young adult female SCA Sprague-Dawley rats received moderate contusion injuries at T9-T10 using the MASCIS weight drop device. One group (n=16) received oral doses of imatinib 30min after injury and then daily doses for 5days. A control group (n=18) received vehicle. Motor function was assessed with the BBB locomotor rating scale and a contact plantar placement task. Bladder function was assessed by measuring the amount of urine retained in the bladder. Tissue preservation was assessed by immunostaining and stereological analysis. Rats that received imatinib had lower volumes of retained urine, suggesting improved bladder function, but there were no significant differences in motor function on any of the other tasks. Tissue preservation was assessed by immunostaining and stereological analysis. Quantitative analysis of spared tissue, cyst size, spared white matter, and inflammatory cell invasion revealed no significant differences between imatinib treated and control rats. Taken together our results confirm the findings that treatment with imatinib improves bladder function after SCI but fail to replicate findings of improved motor function, enhanced tissue sparing, and decreased inflammatory cell invasion.
Reeve-Irvine Research Center, USA.
Kelli G
KG
Sharp
Reeve-Irvine Research Center, USA.
Kelly Matsudaira
KM
Yee
Reeve-Irvine Research Center, USA; Department of Anatomy & Neurobiology, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA; Department of Neurobiology & Behavior, University of California at Irvine, Irvine, CA 92697-4265, USA; Department of Neurosurgery, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA. Electronic address: osteward@uci.edu.
Oswald
O
Steward
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000502:physiology; D000068877:Imatinib Mesylate; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate
Axon regeneration; BBB scale; Bladder function; Contusion injury; Gleevac®; Imatinib; Recovery of function; Spinal cord injury