Prevention of Neurologic Deficit after Acute Spinal Cord Injury
Abstract
The objectives of this proposal are to: ( 1) demonstrate feasibility and proof of principle for reducing spinal cord damage after acute injury using an emergent intravenous pharmaceutitcal of tissue inhibitor ofmatrix-metalloproteinase-3 (TIMP3) (2) demonstrate feasibility and proof of principle for enhancing acute spinal cord injury recovery and healing and reducing long-term paralysis using intravenous administration of banked multipotent adult progenitor cells (MAPCs) and (3) determine ifthe combination ofTIMP-3 and MAPC treatment will further reduce spinal cord damage, enhance axonal regeneration and decrease subsequent paralysis. The proposed studies will utilize a rat spinal cord injury model where the injury is a result of a standardized contusion with an impactor device aimed at the midline of the spinal cord. The impact force will create a severe spinal cord injury without puncturing the cord. After injury, rats will recover from anesthesia and be monitored for 10 weeks. Neurologic status will be monitored weekly by gait analysis, and rated on a locomotor rating scale. The animals will be sacrificed at 10 weeks and histologic studies of the spinal cord performed to assess axonal regeneration, fibrosis and necrosis. Treatment with tissue inhibitor ofmatrix-metalloproteinase-3 (TIMP3) will be administered 1 hour and/or 24 hours post-injury or with multipotent adult progenitor cells (MAPCs) at 24 hours post-injury. The treatment animals will receive either recombinant human TIMP3 (60 µg/kg per dose, IV) or MAPCs at 4x106 cells/250g rat via a tail vein injection. A combination ofTIMP3 and MAPC treatment will be evaluated to determine ifthere is a synergistic treatment effect to establish whether combined administration of TIMP3 and MAPCs is superior to either individual treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 30, 2017
- Source ID
- W911NF1510074
Entities
People
- Kenton Gregory
Organizations
- Army Contracting Command
- Defense Advanced Research Projects Agency
- Oregon Health & Science University