Imatinib Enhances Functional Outcome after Spinal Cord Injury

被引:49
作者
Abrams, Mathew B. [1 ]
Nilsson, Ingrid [2 ]
Lewandowski, Sebastian A. [2 ]
Kjell, Jacob [1 ]
Codeluppi, Simone [1 ]
Olson, Lars [1 ]
Eriksson, Ulf [2 ]
机构
[1] Karolinska Inst, Dept Neurosci, Stockholm, Sweden
[2] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; CELLULAR INFLAMMATORY RESPONSE; ENDOTHELIAL-CELLS; PROGENITOR-CELL; VASCULAR WALL; ACUTE-PHASE; PDGF-CC; RECOVERY; MACROPHAGES;
D O I
10.1371/journal.pone.0038760
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We investigated whether imatinib (Gleevec (R), Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.
引用
收藏
页数:12
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