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SCRF project update.

The following progress reports are of three SCRF-funded research projects. The first is a clinical study to determine whether weight bearing or exercise of paralyzed limbs (induced by functional electrical stimulation) can reduce bone loss after spinal cord injury. Thus far, the results have not shown any reduction in bone loss.

The second study, in basic neuroscience, is an experimental attempt to connect a noninjured nerve to a damaged bladder never. The exciting results are that the nerves have connected and are functional.

The third study, also a basic neuroscience project, discovered that a group of cells in the colon and bladder (called interstitial cells of Cajal, or ICC) can activate muscles of the colon and bladder. Discovery of the electrical activity of these cells may provide a possible new mechanism for controlling bladder and colon muscle in individuals with paralysis.

Clinical Study

"The role of weight bearing and functional electrical stimulation (FES)-induced exercises on bone loss after an acute spinal cord injury"

Researcher: W. Jerry Mysiw, M.D., Ohio State University, Columbus

Purpose: Prominent among the metabolic changes after a spinal cord injury is abnormal calcium metabolism, ultimately resulting in disuse osteoporosis (loss of bone mass associated with physical inactivity). Significant bone loss usually occurs below the level of injury. The objectives of this study are: (1) to determine if bone loss can be prevented by exercises that place mechanical stresses across muscle and bone, (2) to investigate whether bone loss can be reversed by exercise, and (3) to determine the most effective exercise program in preventing bone loss.

Methodology: A group of chronic SCI patients will be placed on an FES-powered cycling exercise program to determine if bone mass can be regained. A group of acute SCI patients will be placed in an exercise program to study the most effective means to prevent disuse osteoporosis. These programs will include weight bearing through quiet-standing and leg-bicycling induced by FES. The effects of these exercises on bone loss will be monitored by biochemical methods and by measurements of bone density.

Progress: Data gathering continues.

Results: Of the ten subjects involved in the chronic SCI study, eight have completed nine months of training. All subjects had evidence of significant osteopenia (reduced bone mass). Although normal parameters of calcium metabolism resulted from the exercise, measurements of regional bone mass revealed no significant changes.

Five studies revealed a significant increase in parathyroid hormone and vitamin D. These data suggest that although leg-bicycling induced by FES can increase bone-cell activity, it is followed by secondary hyperparathyroidism (below-normal serum-calcium levels), which may negate the anticipated increase in bone-mineral density.

To date, 13 subjects have been enrolled in the acute SCI study of leg-bicycling induced by FES. After 12 weeks of training, bone-mineral density at the lumbar spine increased slightly, while losses in bone mass were noted at all other sites. There were no significant changes in serum calcium, phosphate, alkaline phosphatase, or osteocalcin with training. However, urine calcium decreased significantly. These preliminary results suggest that FES cycling appears to have no significant effect on preventing osteopenia but is associated with a dramatic decline in urine calcium excretion (AAPM&R, 1990).

Future Plans/Implications: Studies will be conducted to determine if secondary hyperparathyroidism observed in chronic subjects is reversible.

Publications resulting from this research include:

* "Changes in regional bone mineral density with immobilization due to spinal cord injury." Bloomfield, S. A., W. J. Mysiw, and R. R. Jackson, in American College Sports Medicine, 1990 (Abstract).

* "Can functional electrical stimulation cycle ergometry reverse disuse osteopenia in chronic spinalcord injury?" Bloomfield, S. A., et al., in American Society of Bone Mineral Research, 1990 (Abstract).

* "Effect of functional electrical stimulation calcium and bone metabolism in chronic spinal cord injury." Jackson, R. D., W. J. Mysiw, and S. A. Bloomfield, in American Academy of Physical Medicine & Rehabilitation, 1990 (Abstract).

* "Hypercalciuria but not bone loss is prevented by functional electrical stimulation." Mysiw, W. J., R. D. Jackson, and S. A. Bloomfield, in American Academy of Physical Medicine & Rehabiliation, 1990. (Abstract)

Basic Neuroscience Studies

"Bladder reinnervation by anastomosis of L4 VR to L6 VRwhile leaving intact L4 DR as starter of micturition"

Researcher: Chuanguo Xiao, M.D., Eastern Virginia Medical School, Norfolk

Purpose: The objective of this project is to establish an alternative reflex pathway (skin-central nervous system-bladder) for micturition (urination). In most spinal cord injured individuals the normal reflex pathway (bladder-central nervous system-bladder) has been severely damaged. A new pathway would bring micturition under voluntary control, with the individual initiating voiding by scratching the skin.

Methodology: In rats, the motor nerve of a normal reflex arc above the injury (L4 VR) will be connected to the motor nerve leading to the bladder, below the injury (L6 VR), while leaving the intact sensory root (L4 DR) as a starter of micturition. After three months of regeneration, the new pathway will be studied electrophysiologically and anatomically to determine if the new pathway is functional.

Progress: The new reflect pathway has been successfully established and is functionally effective in the rats.

Results: The results demonstrated that the motor root above the spinal micturition center can be used to reinnervate the bladder, and that the axons can regenerate to at least as far as the pelvic ganglia.

Future plans/implications: These results have strong potential for clinical application in patients with neuropathic bladders. A future study will be conducted on higher-level mammals. In addition, it may be possible for similar pathways to be developed for other applications to problems caused by disease or injury to the spinal cord.

"Electrophysiological basis for contraction in the bladder"

Researcher: Kenton M. Sanders, Ph.D., University of Nevada School of Medicine, Reno

Purpose: To characterize the activity of interstitial cells of Cajal (ICC), which are hypthesized to be to pacemaker cells, and which are found in colon and bladder muscles. Such pacemaker cells could be important in activating colon and bladder muscles for defecation and urination. Additionally, the study will determine the effects of various drugs on the rhythmic electrical activity of ICC, essential for normal motor functioning of the colon and bladder.

Methodology: ICC from colon and bladder of dogs were identified, and the electrical excitability of these cells was studied. Experiments were performed to determine whether isolated ICC were capable of spontaneous rhythmic activity. In addition, whole bladder studies were conducted using standard electrophysiological techniques.

Progress: The studies described in the above methodology section have been performed.

Results: Electrical recordings from ICC indicated they were indeed electrically active, producing a series of rhythmic electrical events. This finding is extremely significant, because it means that certain groups of cells are responsible for the contraction of colon and identifiable bladder muscle.

Future plans/implications: To further characterize the role of ICC in generating electrical activity in the bladder. The results of this project should help scientists develop new drugs for treating individuals with colon and bladder problems.
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Title Annotation:Spinal Cord Research Foundation
Author:Chanaud, Cheryl M.
Publication:PN - Paraplegia News
Date:Dec 1, 1990
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