A re-assessment of treatment with a tyrosine kinase inhibitor (imatinib) on tissue sparing and functional recovery after spinal cord injury.

Experimental Neurology(2014)

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摘要
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.
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关键词
Spinal cord injury,BBB scale,Imatinib,Gleevac®,Axon regeneration,Contusion injury,Recovery of function,Bladder function
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