PHYSICAL PROPERTIES OF LAMPREY SPINAL CORD REGENERATION : ADAPTIVE VS . MALADAPTIVE RECOVERY Carlos

Title of Document: PHYSICAL PROPERTIES OF LAMPREY SPINAL CORD REGENERATION: ADAPTIVE VS. MALADAPTIVE RECOVERY Carlos Luna Lopez, Ph. D., 2014 Directed By: Associate Professor, Helim Aranda-Espinoza, Fischell Department of Bioengineering Spinal cord injury (SCI) is a physical trauma that can result in paralysis and even death; to date no treatment exists that can successfully promote functional or adaptive recovery. Although humans are unable to regenerate after complete SCI, there are animal models that have been studied for their ability to regrow and reconnect their nerve fibers. From the group of animals that are capable of spinal cord regeneration, in the best studied is the lamprey (Petromyzon Marinus) it has been noted that recovery can be maladaptive. When left to recover at warm temperature (23 0C) most lampreys had adaptive behavior, but at cold temperature (10 0C) most lampreys showed maladaptive behavior. In this dissertation we studied the physical factors that influence adaptive and maladaptive recovery in lampreys. In the first part, we analyzed axonal regeneration and blood clot formation at early time points after injury (1-2 weeks). We found that lampreys in cold temperature have a blood clot that could be blocking spinal cord regeneration. In the second part of this work, we analyzed the biomechanical and structural differences between lampreys in warm and cold temperature. We used in vivo X-ray imaging and tensile loading testing of the spinal cord and notochord structures, before and after injury. We found that lampreys at warm temperature are more favorable to create a permissive mechanical and structural environment for regeneration. Lastly, we used those lessons learned previously to enhance regeneration of maladaptive animals. We removed the blood clot at the injury site and created a time frequency analysis to measure the recovery of coordination. We found that lampreys in cold temperature with clot removal had a more adaptive recovery after injury than those without removal. In summary, by using the lamprey we were able to compare the differences between regeneration in warm and cold temperature and found the physical factors that influence maladaptive recovery. Removing one of these factors, in this case the blood clot, successfully enhanced the recovery of coordination. These results have the potential to be translated to higher animals and aid in the creation of successful