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Proquest Dissertations INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may t>e from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistsict print, colored or poor quality illustrations and photographs, print Meedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will b e noted. Also, if unauthorized copyright material had to t>e removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced t)y sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black arxf white photographic prints are available for any photographs or illustrations appearing in this copy tor an additional charge. Contact UMI directly to order. Bell & Howell Information and Learning 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA UIVLI800-521-0600 THE RECOVERY OF FUNCTION AFTER SPINAL CORD CONTUSION INJURY IN RATS: SKELETAL MUSCLE, NEURAL, AND BEHAVIORAL ADAPTATIONS WITH AND WITHOUT EXERCISE DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Karen J. Hutchinson, M.S., P.T. ***** The Ohio State University 2000 Dissertation Committee: Dr. D. Michele Basso, Adviser Approved by Dr. James S. King, Co-Adviser Dr. Jacqueline C. Bresnahan Adviser Dr. Jon K. Linderman Neuroscience Graduate Program UMI Number 9962402 UMI* UMI Microform9962402 Copyright 2000 by Bell & Howell Information and teaming Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. Bell & Howell Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Spinal cord injury (SCI) can result in significant and long lasting functional motor deficits. In our first study, we evaluated one parameter that may influence motor recovery following spinal cord injury; hindlimb (HL) skeletal muscle. Changes in skeletal muscle properties appear to parallel the functional status of the animal. For example, early after SCI, the animal presents with significant hindlimb paralysis/ paresis, as well as, significant muscle atrophy. Over a 10 week period, muscle atrophy is attenuated corresponding to improved HL movement and locomotor activity. In a second study, we examined the effect on locomotion of three exercise paradigms designed to maximize rhythmicity, weight bearing (WB) or both in the hindlimbs after SCI. Groups were trained to swim (rhythmicity, no WB), stand (WB, no rhythmicity), and treadmill step (rhythmicity and WB). Early significant locomotor improvements were identified for swim and treadmill training. Surprisingly, greater residual deficits occurred after stand training, suggesting that WB alone is insufficient to improve locomotion. Furthermore, SCI heightens reflex responses and lowers thresholds to somatosensory stimuli caudal to the injury. Exercise training (particularly treadmill) appeared to normalize sensation as shown during flexor withdrawal and von Frey hair testing. Engaging in early, moderate exercise after SCI also did not exacerbate lesion size as has been described for brain injury. Lastly, immunohistochemical and gel electrophoresis techniques determined that these exercise induced sensory and motor changes were not accompanied by changes in muscle fiber composition or size of a locomotor-related muscle of the hindlimb, the slow twitch soleus. lU DEDICATION I would like to dedicate this work to two very important people in my life. First, to my soul mate and partner of several years, Edward T. Hutchinson. Your constant support and encouragement have made the impossible seem probable; the stress seem manageable; and the goal attainable. This document / achievement would not have happened without you. Secondly, to my best fiiend 6om childhood, M.M.D., whose daily struggle with paralysis is overshadowed by her grace and dignity. For 17 years I have wimessed the strain that this injury places on the personal, professional and social lives of its victims. The challenge of finding a “cine” should never be defeated by the tribulations associated with the effort. IV ACKNOWLEDGMENTS Many thanks go out to several people who helped me to make this publication possible. To Lesley Fisher who assisted in virtually all aspects of this research, fix>m animal training to spinal cord tissue processing, I am eternally grateful. Special thanks go to Dr. B. Stokes and Dr. Lyn Jakeman for use and training on the MCID image analysis system that allowed me to use sophisticated ‘state of the art’ computer software to analyze spinal cord and skeletal muscle tissue. Thank you also to Tina Van Meter whose patience and instruction was invaluable for cryostat sectioning of fresh unfixed muscle samples and to Amy Tovar whose assistance in animal testing allowed me to stay “masked” to the animal testing condition. Also, thank you to John Komon for instruction on the use of the stereologer, to Pat Walters for her dedication to excellent animal care and to Amy Lindsay for teaching me the von Frey Hair testing protocol. Dr. Larry Sachs and Dr. John Buford were invaluable resources for the data analyses included in these studies. I would also like to thank my committee; Dr. J. Linderman, Dr. J. Bresnahan, and Dr. J. King for giving me faith and respect for the academic process. Finally, a special thanks goes out to my advisor. Dr. Michele Basso, for her vision, inspiration and constant dedication to the cause. It was through the course of many fruitful discussions that lead to the development of the ideas contained in this document. VITA June 4 ,1 9 6 4 ..........................Bom in Boston, MA 1982-1986 ...............................B.S., Physical Therapy The University of Lowell, Lowell, MA 1986 —1990.............................Staff Physical Ther^ist/Resource Clinician Inpatient and Outpatient NeurorehabiUtation Braintree Hospital 1990-1993...............................M.S., Physical Therapy Division of Physical Therapy, School of Allied Medicine The Ohio State University, Columbus, OH 1993-199 4.............................. Graduate Research Associate Neuroscience Program, Department of Psychology The Ohio State University, Columbus, OH 1994-199 6.............................. Graduate Research Associate Neuroscience Program, Department of Psychobiology The Ohio State University, Columbus, OH 1996-Present.......................... Graduate Research Associate Neuroscience Program, Department Cell Biology, Neurobiology and Anatomy The Ohio State University, Columbus, OH PUBLICATIONS Research Publication 1. DS Nichols, TMGlenn, KJ Hutchinson. Changes in the mean center of balance during balance testing in young adults. Physical Therapy, 75(8): 699-706, (1995). VI Published Abstracts 1. K Hutchinson, J Vensel, S Obermiller, L LeDufF, L Fisher, DM Basso. Early moderate exercise training after spinal cord injury does not exacerbate lesion size and attenuates changes in hindlimb sensation in the rat. Society for Neuroscience, 25:110, (1999). 2. KJ Hutchinson, LC Fisher, MB Johnson, J Linderman, DM Basso. Moderate exercise training improves locomotor recovery and does not exacerbate lesion size when implemented early after spinal cord injury in rat. Neurology Report, 22(5):181- 182, (1998). 3. CA Voll, Jr, LC Fisher, KJ Hutchinson, DM Basso. The severity of hypeireflexia is greater after moderate vs. mild experimental spinal cord injury in rats. Neurology Report, 22(5): 174, (1998). 4. MJ Crowe, KJ Hutchinson, DM Basso. Neurotrophin and insulin-like growth factor-1 mRNA expression in rat hindlimb muscles after spinal cord injury. Society for Neuroscience, 24(1):1149, (1998). 5. K Hutchinson, L Fisher, J Linderman, DM Basso. Exercise training improves recovery firom spinal cord contusion injury in the rat. Society for Neuroscience, 24(2): 1415, (1998). 6. K Hutchinson, J Linderman, DM Basso. Relationship between behavioral recovery, muscle structure and muscle ftmction after spinal cord injury in rat. Neurology Report, 21:175, (1998). 7. K Hutchinson, J Linderman, DM Basso. Effects of experimental spinal cord injury on behavior and hindlimb muscle ftmction in rat. Journal of Neurotrauma, 14:782, (1997). 8. K Hutchinson, J Linderman, DM Basso. Effects o f experimental spinal cord injury on hindlimb skeletal muscle in rat. Society for Neuroscience, 23:2190, (1997). 9. K Hutchinson, J Linderman, DM Basso. A comparison of Fischer 344 and FI Hybrid rats for appropriate animal models for neuromotor control and aging. Neurology Report, 20(4):15-16, (1996). vu 10. K Hutchinson, M Sarter, B Givens. Single unit activity in medial prefirontal cortex of rats performing in a behavioral vigilance task. Society for Neuroscience, 22:1388, (1996). 11. DS Nichols, KJ Hutchinson, LA Colby. Reliability and validity of the CTSIB and Chattex Balance System in the evaluation of individuals with hemiparesis. Society for Neuroscience, 21(2):1203, (1995). 12. B Givens, K Hutchinson, K McMahon.
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