Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers
| Autor: | Zsuzsanna Wiesenfeld-Hallin, Ulf Eriksson, Jacob Kjell, Camilla I. Svensson, Lars Olson, Anna Josephson, Mathew Abrams, Katrin Wellfelt, Anja Finn, Jing-Xia Hao |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Chemokine
Time Factors glivec chemokines Hindlimb Rats Sprague-Dawley hemic and lymphatic diseases medicine Animals bladder function Spinal cord injury Protein Kinase Inhibitors Spinal Cord Injuries biology business.industry Imatinib locomotor function Original Articles Recovery of Function Functional recovery medicine.disease cytokines Rats Disease Models Animal Imatinib mesylate Anesthesia Acute spinal cord injury biology.protein Imatinib Mesylate Female Neurology (clinical) business Bladder function Biomarkers medicine.drug |
| Zdroj: | Journal of Neurotrauma |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. |
| Databáze: | OpenAIRE |
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