1998 — 2002 |
Roy, Roland R |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Animal Care @ University of California Los Angeles
The Animal Core is designed to: 1) provide the care and maintenance of all animals used in the PPG; 2) provide assistance in all surgical and training procedures required in the PPG; and 3) maintain an updated database on the health status of the rats and post-mortem tissue distribution. These activities are very demanding with respect to the expertise required and the level of coordination necessary among the Principal Investigators, Animal Health Technician and Division of Laboratory Animal Medicine (DLAM). The amount of care and time required and the still that is essential in maintaining optimum health of spinal cord isolated and spinal cord transected rats is also quite demanding. Care and treatment interventions must be uniform and consistent and the general health of the animal must be maintained at the highest level. It is critical to maintain the high quality of care for spinal cord injured animals that we have developed over the years. This experience and the cooperative efforts between Dr. Roy, the PI of this Core, Ms. Laurentz, the Animal Health Technician responsible for the day-to-day animal care, and DLAM, has proven to be extremely effective and must be maintained to assure the success of Projects. The Core personnel will also assure that all individuals that work directly with the animals are properly trained and supervised in animal care procedures. An animal core is the best mechanism to accomplish these objectives. With an individual R-01 grant it would be difficult to provide the quantity of personnel necessary with the required skill level to study spinal cord injured animals.
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1998 — 2002 |
Roy, Roland R |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Plasticity of Inactive Mammalian Skeletal Muscle @ University of California Los Angeles
Multiple factors determine whether the net synthesis of proteins and mass of skeletal muscle fibers increase, decrease of remain constant. The primary objective of this proposal is to determine the contribution of neural (activity-independent neurotrophic) and mechanical (tension) factors as independent and as interactive factors in maintaining the functional, structural and metabolic integrity of skeletal muscles that have been subjected to 60 days of complete inactivity. Whole muscle and single fibers in the adult rat soleus, a slow extensor known to be affected dramatically by decreased used, will be studied. A unique aspect of the proposal is that a true baseline of inactivity will be produced by spinal cord isolation (SI), i.e. spinal cord transection at a mid-thoracic and high sacral level and bilateral dorsal rhizotomy between the two transection sites. In one group of rats, intramuscular electrodes will be implanted in several hindlimb muscles to monitor EMG activity throughout the experimental period. To define the level of control attributable to activity-independent neurotrophic factors, a section of the lateral gastrocnemius-soleus nerve will be removed in some groups of SI rats. In some SI rats, stimulating electrodes will be implanted near the lateral gastrocnemius-soleus nerve (nerve-intact group) to isometrically stimulate (40 Hz, 330 ms train, once/second) the soleus twice daily for 30 minute/session. Tendon force transducers will be implanted acutely on the distal soleus tendon to quantify the forces imposed on the muscle during the stimulation protocol. After 60 days, contractile, morphological, biochemical and/or histochemical properties of the whole muscle and/or single fibers will be determined. The regulation of type I myosin heavy chain gene expression at the transcriptional-pretranslational level associated with SI and/or denervation, with and without mechanical stimulation, will be determined 28 days after SI. Since fiber size can be modulated concomitantly with the number of myonuclei, the role of apoptosis, i.e. programmed cell death, and satellite cell activity in the atrophic response and the expected amelioration of atrophy with resistance exercise will be determined at two time points, i.e. 8 and 17 days after SI. In these studies we will identify the relative importance of the control of muscle mass and phenotype from a) within the muscle fiber (intrinsic, no neurotrophic); b) the nerve supply without activity (neurotrophic); and c) the nerve supply with controlled activity and force patterns. Clinically, the results will demonstrate the efficacy of short, daily periods of programmed mechanical stimulation as a preventative and/or rehabilitative tool for patients with spinal and neuromuscular maladies.
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2003 — 2007 |
Roy, Roland R |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Animal Core @ University of California Los Angeles
The Animal Core is designed to: 1) provide optimum care and maintenance of all animals used in the PPG; 2) provide assistance in all surgical procedures required in the PPG; 3) provide support for and supervision of the step training and robotic testing of spinal transected rats (Projects II and III), spinally injured mice (Project IV) and the electro-mechanical stimulation of the muscles in spinal cord isolated rats (Project I); and 4) maintain an updated database on the health status of the rats and post-mortem tissue distribution. These activities are very demanding with respect to the expertise required and the level of coordination necessary among the Principal Investigators, Animal Health Technician and Division of Laboratory Animal Medicine (DLAM). The amount of care and time required and the skill that is essential in maintaining optimum health of spinal cord isolated and spinal cord transected rats is also quite demanding. Care and treatment nterventions must be uniform and consistent and the general health of the animal must be maintained at the highest level. It is critical to maintain the high quality of care for spinal cord injured animals that we have developed over the years. This experience and the cooperative efforts between Dr. R.R. Roy, the PI of this Core, Mr. M. Herrera, the Animal Health Technician responsible for the day-to-day animal care, and DLAM, has proven to be extremely effective and must be maintained to assure the success of Projects I, II, III, and IV. The Core personnel also will assure that all individuals that work directly with the animals, to include graduate and undergraduate students, are properly trained and supervised in animal care procedures. The robotic testing of the behavioral capabilities of the spinal transected rats is a unique and crucial element for the success of Projects II, III and IV. Dr. D. Reinkensmeyer (UCI) will coordinate the development and building of the robotic systems and Ms. R. Molyneux will supervise and assist in all aspects of the robotic-related studies at UCLA. An animal core is the best mechanism to accomplish these objectives. With an individual R-01 Grant it would be difficult to provide the quantity of personnel necessary with the required skill level to study spinal cord injured animals.
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2003 — 2007 |
Roy, Roland R |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Use Dependent Molecular Modulation of Rat Hindlimb Muscles @ University of California Los Angeles
The mechanisms of skeletal muscle atrophy, and the associated functional deficits, produced by a chronic decrease in the levels of neuromuscular activity are not well defined. Similarly, the most efficacious type or quantity of electro-mechanical activation to use as a countermeasure for these detrimental effects are undefined. We are proposing to use a model of virtually complete inactivity while preserving neurotrophic support, i.e., spinal cord isolation (SI), to address these issues. SI involves complete spinal cord transections at a mid-thoracic and high sacral level and bilateral dorsal rhizotomy between the two transection sites. SI, therefore, provides a baseline for determining the effects of chronic inactivity on skeletal muscle. We have successfully used a battery of molecular markers for protein metabolism to identify some of the major pathways involved in the skeletal muscle hypertrophic response associated with the functional overloading of a muscle by removal of its major synergists. These results have provided a framework for identifying the major pathways associated with muscle atrophy. Our overall working hypothesis is that the elimination of the normal activation/loading parameters on a muscle will down-regulate the pathways that have been shown to be up-regulated with increased activation/loading. We then will use high resistance isometric regimes to counteract the detrimental effects of inactivity on muscle function and phenotype. A unique BION stimulation implant system will be used to impose a known amount of electro-mechanical stimulation on the otherwise "silent" plantarflexor muscles. Our approach will be to begin to identify the optimum stimulation paradigms for maximum maintenance of the properties of both a slow and a fast plantarflexor. We will vary the patterns of stimulation to optimize the normal contractile dynamics of each of these muscle types and will determine the effectiveness of imposing these electro-mechanical regimes once vs. twice per day. We will identify molecular mechanisms which can be used to counter the atrophic response. From a clinical perspective, understanding how critical molecular events can be modulated by known quantities of electro-mechanical stimulation will provide a clear direction for designing exercise and programmed mechanical stimulation paradigms to be used as preventive and/or rehabilitative tools for patients with muscle atrophy associated with spinal and neuromuscular maladies, aging, etc.
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