Imatinib enhances functional outcome after spinal cord injury.
We investigated whether imatinib (Gleevec®, 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.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. mathew.abrams@ki.se
Mathew B
MB
Abrams
Ingrid
I
Nilsson
Sebastian A
SA
Lewandowski
Jacob
J
Kjell
Simone
S
Codeluppi
Lars
L
Olson
Ulf
U
Eriksson
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001549:Benzamides; D001812:Blood-Brain Barrier / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000068877:Imatinib Mesylate; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000534:rehabilitation*; D016896:Treatment Outcome
D001549:Benzamides; D011508:Chondroitin Sulfate Proteoglycans; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor