Outcome Measure Studies
Objectives: To develop new relevant methods for assessing functional recovery following spinal cord injury, including locomotor behavior, fine motor control of the forelimb, and bladder function.
Assessing Locomotor Behavior
When a new spinal repair strategy is attempted in rodents, it is usually evaluated by visually observing and rating the locomotor behavior of the animals (BBB scale, grid walk, narrow beam). While these observational tests provide insight into recovery, they provide sparse information about the detailed biomechanics and neuromuscular control of the movement recovery. In some experiments hand digitization of leg kinematics from video or footprint analysis or kinetic data from force sensors embedded in a runway used to provide more detailed insight into the recovery biomechanics. However, these techniques are time consuming and are not widely used. In addition, there are currently few or no techniques for quantifying the effect of loading on locomotor ability. For example, no technology exists for precisely varying the weight support provided during locomotor testing. As a result, neural repair techniques that have a beneficial effect on locomotor pattern generation may, for example, be misconstrued as ineffective because their benefits are masked by still-impaired postural control mechanisms.
Dr. Reinkensmeyer's laboratory at UCI in collaboration with Dr. Edgerton's laboratory at UCLA and Dr. de Leon's laboratory at CSU Los Angeles have developed two generations of robotic devices (called "steppers") for studying stepping in rats and mice. Both generations make use of lightweight robotic arms that attach to the animal's hindlimbs. A body weight support mechanism (BWSM) stabilizes and supports the animal's torso, and partially unloads the limbs as the animal steps on a treadmill. The robot arms record the limbs' motion during stepping and can apply forces to assist or perturb stepping. The limbs' motion is recorded at a high sampling rate (100 Hz) with high position resolution (< 0.1 mm), so a detailed spatiotemporal picture of the stepping trajectory can be generated. In the present project, Dr. Reinkensmeyer's group is developing a standardized protocol for assessing hindlimb function after spinal cord injury.
Assessing fine motor control of the forelimb
A second goal of the RIRC's FOR-SCI outcome measures contract is to develop simple, reliable, quantitative assays of forelimb function in rats, that can be used by the entire spinal cord research field to examine the functional losses and recovery of function of forelimb digital flexors following a cervical SCI. We are especially interested in developing reliable and relatively straightforward ways to rapidly assess forelimb function in a longitudinal fashion using a technique that has the same general advantages as the BBB for locomotor function.
We are developing a battery of behavioral tests to examine functional loss after cervical SCI, and to define both the acute and chronic deficits to establish a baseline for analyzing any effects of future treatments. The optimal behavioral test designed to assess forelimb function should conform to the following criteria in order to be utilized across laboratories: 1) simple to administer, 2) reliable and reproducible, 3) objective, 4) quantitative, 5) non-invasive, 6) relatively easy to relate to brain and spinal cord circuitry, and 7) relevant to humans. In this regard, the fine motor control of the digits of the forelimb is of special relevance, especially because rats use their "hands" for grasping and manipulating in much the same way that a human does. Behavioral tests will be designed to analyze the forelimb deficits resulting from a cervical hemisection.
Assessing bladder function
The third goal of the RIRC's FOR-SCI outcome measures contract is to develop a bladder function assessment scale for rats. When spinal cord injured patients are asked to identify the most serious problems that they face in daily life, and what they would most like to improve, a common answer is bladder function. Bladder malfunction and urinary tract infections are probably the most common causes of serious illness in SCI patients. Treatments that produce even minor improvements in bladder function could be of immense benefit to the patient.
It is critical to routinely assess bladder function in experimental animals after spinal cord injury, because it is quite possible that treatments that have minimal impact on locomotor or other obvious motor function could vastly improve bladder function. We propose to develop an easy, reliable assessment scale for bladder function that could be applied across labs in much the same way that the BBB assessment has become the standard for assessing locomotor function.