TY - JOUR TI - The Fischer 344 spinal cord contusion model and effects of cyclosporin-A on the model DO - https://doi.org/doi:10.7282/T35X2C3M PY - 2016 AB - The Multicenter Animal Spinal Cord Injury Study (MASCIS) standardized spinal cord injury (SCI) in Long-Evans hooded and Sprague-Dawley rats. In this thesis, we extended the MASCIS model to Fischer 344 (F344) rats for the following reasons. First, F344 rats are immune-compatible with each other. Cells can be transplanted from one F344 rat to another without immunosuppression. Second, our laboratory developed a strain of F344 rats that express green fluorescent protein (GFP). When transplanted into regular F344 rats, GFP F344 rat cells can be readily identified. Third, F344 rats are isogenic. They should have more uniform and replicable responses to injury and therapies. Finally, this F344 model allows us to assess effects of allogeneic cell transplants with and without immunosuppressive drugs, such as cyclosporin-A (CsA), as well as the effects of immunosuppressive drugs on transplanted cells. We chose to assess olfactory ensheathing glial (OEG) cell transplants because many investigators have reported that these cells improve motor recovery in rat SCI models. Our results show that F344 rats can be reproducibly injured with the MASCIS model and that OEG transplants significantly improve locomotor recovery when transplanted without CsA. However, we encountered several unexpected findings. Female rats recovered more than male rats even though the animals were age-matched, studies of the spinal cords revealed no difference in size and anatomy of age-matched male and female rats, and 24-hour lesion volumes in male and female spinal cords were the same. OEG transplants improved recovery of male rats, almost as well as untreated female rats. CsA therapy improved recovery in both male and female rats. We conclude that the MASCIS model causes reproducible injury to spinal cords of F344 rats, age-matched female rats recover better locomotor function than male rats, OEG cells can be transplanted from GFP F344 rats to wild-type F344 rats without immune rejection, OEG transplants improve functional recovery particularly in male rats, CsA improved locomotor recovery in both male and female F344 rats. The MASCIS impactor model should be very useful for assessing mechanisms underlying gender differences, OEG and CsA effects on transplanted cells and recovery mechanisms. KW - Neuroscience KW - Cyclosporine KW - Spinal cord--Wounds and injuries LA - eng ER -