This study will investigate the effects of a robotic gait training algorithm on the preservation of lower extremity muscle mass and strength, and the molecular mechanisms involved in skeletal muscle atrophy/hypertrophy in the rat model of spinal cord injury (SCI).
The research objectives for this project are:
1. Develop a novel version of the rat stepper that includes force sensors to measure interaction forces between the device and the animal.
2. Examine the effects of using a robotic training algorithm to increase plantarflexion torque during stance in spinal cord injured rats.
3. Examine the effects of eight weeks of robotic gait training on hindlimb muscle mass, crosssectional area, and the atrophy/hypertrophy molecular signaling cascades following SCI.
Locomotor training will be performed using a specially designed, robotic gait device, patterned after a previous model developed by the PI (i.e. the 'rat stepper'). Select modifications to this device will make possible the measurement of interaction forces between the animal and the robot, as well as muscle forces generated during stepping. Muscle strength will be measured in vivo as the animal steps in the robotic device using inverse dynamic techniques. In vitro measures of muscle function will include muscle mass, cross-sectional area, and molecular signaling cascades related to skeletal muscle atrophy/hypertrophy.
SIGNATURE
Marshall M. Lih Senior Advisor, CBET Interim Program Officer, RAPD
Spinal cord injury (SCI) typically results in a reduced ability to initiate and control movement, which often leads to changes in muscle function due to periods of inactivity. There is currently a need for research that can inform the development of rehabilitation strategies to promote the preservation of muscle function following SCI. This research project was designed to address this need by investigating the effects of robot-applied walking therapy on the health and function of leg muscles in rats with a spinal cord injury. In pursuit of this objective, a robotic device that can apply this type of therapy was fabricated and tested, with miniature force sensors attached to portions of the robot that interact with the stepping animal. Several animals were trained daily for up to eight weeks in this manner while detailed information about the quality of their leg movements was recorded by the robotic device. In addition, tissue samples from the animals’ hindlimb muscles were carefully collected and stored at the end of their training period for analysis of molecular and genetic changes that occurred as a result of this type of walking activity. To date, this work has generated multiple findings, but two primary findings are highlighted here. First, this work has demonstrated the feasibility of measuring animal-robot interaction forces as a means to assess recovery following SCI, to dose the intensity of therapy, and to distinguish between animals that have received training and those that have not. Because rats are one of the most widely used methods of studying SCI, this information will help others who perform similar research. Second, this work has provided important insight to understanding the application of load to an animal’s hindlimb during therapy. Persons with SCI who undergo this type of walking therapy often require that a portion of their body weight be unloaded in order to assist them with stepping. While necessary in many cases, this practice may lead to suboptimal outcomes in terms of leg strength because muscles are not sufficiently loaded. In the rat model, we attempted to correct for this decrease in load by programming the miniature robotic arms to push down on the rats’ hindlimbs at important points in the step cycle, thereby increasing the load experienced by the hindlimb muscles. This technique resulted in significant increases in both muscle mass and strength when compared to other types of training. At the time of this report, over 500 tissue samples have been collected and are currently under analysis to determine the molecular and genetic effects of robot-applied therapy on muscle function. Several results from these analyses are still forthcoming. In addition, the immense bank of tissue harvested here, which also includes bone and spinal cord material, can be used for many future experiments. Further, the robotic device can be used to study other important aspects of this type of therapy, and can be easily transported and shared among other researchers interested in similar work. With regard to education, this project has contributed to novel teaching and research opportunities for students at two public Universities that are designated as Hispanic Serving Institutions. In particular, these opportunities have enhanced the careers of four promising young scientists who have continued on to pursue graduate work in similar disciplines. Finally, several presentations and demonstrations of the robotic device have been given as a means to build interest in scientific research and technology and to recruit underrepresented students from several local high schools and community colleges.
