ALTERED INTERMUSCULAR FORCE FEEDBACK AFTER SPINAL CORD INJURY IN CAT A Thesis Presented to The Academic Faculty By Irrum Fawad Niazi In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Applied Physiology Georgia Institute of Technology August 2015 Copyright 2015, Irrum Fawad Niazi ALTERED INTERMUSCULAR FORCE FEEDBACK AFTER SPINAL CORD INJURY IN CAT Approved by: Dr. T. Richard Nichols, PhD, Advisor Dr. Lewis A. Wheaton, PhD. School of Applied Physiology School of Applied Physiology Georgia Institute of Technology Georgia Institute of Technology Dena R. Howland, PhD Dr. Boris I. Prilutsky, PhD Kentucky Spinal Cord Injury Research School of Applied Physiology Center, Department of Neurological Georgia Institute of Technology Surgery University of Louisville Dr. Shawn Hochman, PhD Dr. Young-Hui Chang, PhD Department of Physiology School of Applied Physiology Emory University School of Medicine Georgia Institute of Technology Date Approved: 07/ 22/ 2015 “In all things of nature there is something of the marvelous” (Artistotle) Dedicated to my father and my husband, who allowed me to spread my wings and test my limits ACKNOWLEDGEMENTS They say it takes a village to raise a child. The work presented in this dissertation would not have been possible without the help and support of many individuals. Foremost, I would like to express my sincerest gratitude to my advisor, Dr. T. Richard Nichols, Ph.D., for his continuous support during my doctoral studies and research. He provided a strong foundation for my graduate school experience by letting me explore beyond the textbooks and clinic. I feel extremely lucky to know him as a scientist and a very humble human being. His patience, motivation, enthusiasm and immense knowledge helped me in the entire period of research and writing of this thesis. His support through the tough times and belief in me gave me the strength to continue through my second round of the roller coaster ride of a graduate career. Thank you and Patricia for welcoming Fawad, our triplet daughters and me into your lives through these years. I cannot imagine having a better advisor, mentor and a loving family away from home during my Ph.D. studies in the USA. Thanks to my committee members who have given their time and energy to help me transform from a clinician to a scientist. I especially thank Dr. Dena Howland, Ph.D., for her immense support through these years. You are an amazing researcher, dexterous surgeon and a role model. Thank you for bringing all the amazing animals to our laboratory and sharing your wisdom and knowledge with us. Many thanks to Dr. Boris I. Prilutsky, Ph.D., for always being willing to help and provide best suggestions; Dr. Lewis Wheaton, Ph.D., for inspiration and support to encourage new researchers with an open mind and a generous smile; Dr. Young-Hui Chang, Ph.D., for enthusiasm for science and iv innovation to inspire new scientists to think outside the box; Dr. Shawn Hochman, Ph.D., for input regarding many possible ways to make the project successful. Your knowledge, professionalism, wit and passion for science have always inspired me. To the many current and past members of the Nichols laboratory who have been friends, colleagues and a family through the years. Thank you for your support and guidance. Special thanks to Dr. Mark Lyle, Ph.D., for continued response to my technical emergencies; Gareth Guvanasen for making me laugh while keeping me focused during long experiments; Elma Kajtaz for always providing comic relief and being my family at Georgia Tech; Bill Goosby for honoring my technical support requests; Dr. Victoria Stahl, Ph.D., Dr. Ramaldo Martin, Ph.D., and Chris Tuthill for help and support; and to the faculty, Applied Physiology Department, Georgia Institute of Technology for shaping my carrier as a scientist. I would like to thank my Mom and Dad for believing in me throughout my carrier. I love you dad and will continue my quest to understand the complexities of brain, in remembrance of your untiring battle with brain tumor and quadriplegia. I would like to thank my triplet daughters Zaina, Sibel and Alishba. Your fight against prematurity and your beautiful smiles have given me a new strength in life. Without doubt, having them after 15 years of struggle will stay as the best memory of my graduate school for years to come. I would especially like to thank and honor my angel daughter, Sibel, for inspiring me to keep my faith in life. v Finally, I would like to thank my dear husband Dr. Fawad Niazi, Ph.D. You have always supported and loved me as my best friend. Your unfailing belief that I can achieve anything made me a strong woman through our years of married life. You made me laugh in the toughest of personal and professional times. Your patience and understanding make me feel truly blessed for being married to you for the last 18 years. I truly consider you to be the best gift. I love you always and forever! v i TABLE OF CONTENTS Page ACKNOWLEDGEMENTS iv LIST OF TABLES x LIST OF FIGURES xi LIST OF SYMBOLS AND ABBREVIATIONS xxii SUMMARY xxiii CHAPTER 1: INTRODUCTION 1 1.1 Properties of muscular system 3 1.2 Hind limb ankle extensors 6 1.3 Brain, Brain Stem and Reticular Formation Role in Balance Control and Intermuscular Force Feedback Gradient 7 1.4 Spinal cord role in maintenance of posture 10 1.5 Spinal cord injury 10 1.6 Aims, objectives and hypothesis 13 CHAPTER 2: PATTERNS OF HETEROGENIC FORCE FEEDBACK BETWEEN ANKLE EXTENSORS IN DECEREBRATE CATS 18 2.1 Introduction 18 2.2 Methods 20 2.2.1 Preparation 20 2.2.2 Data Acquisition 24 2.2.3 Data Analysis 25 2.3 Results 27 2.3.1 Force feedback inhibition between GA and FHL 28 vi i 2.3.2 Weak Inhibition is exchanged between FHL and SOL 36 2.3.3 FHL contributes inhibition to PLT 38 2.3.4 Latency of Reflex interactions 40 2.4 Discussion 41 CHAPTER 3: ALTERED PATTERNS OF INTERMUSCULAR FEEDBACK BETWEEN HINDLIMB ANKLE EXTENSORS FOLLOWING CHRONIC SPINAL CORD INJURY IN THE CAT. I. Gastrocanemius and Flexor Hellucis Longus 47 3.1 Introduction 47 3.2 Methods 50 3.2.1 Preparation 50 3.2.2 Data Analysis 57 3.3 Results 63 3.3.1 GA weakly inhibits FHL following chronic SCI 65 3.3.2 FHL strongly inhibits GA following chronic SCI 74 3.3.3 The pattern of inhibitory force feedback across limbs and animals between GA and FHL following chronic LSH 82 3.3.4 Recipient muscle force response depends on the background force of the donor muscle across limbs and animals between GA and FHL following chronic LSH 88 3.3.5 Intermuscular force feedback interactions between FHL and GA in acute spinal cord injury in cat 92 3.3.6 Clasp knife inhibition 97 3.4 Discussion 99 CHAPTER 4: ALTERED PATTERNS OF INTERMUSCULAR FORCE FEEDBACK BETWEEN HINDLIMB EXTENSORS FOLLOWING CHRONIC SPINAL CORD INJURY IN THE CAT. II Soleus, Plantaris and Flexor Hellucis Longus 105 vi ii . 4.1 Introduction 105 4.2 Methods 107 4.2.1 Preparation 107 4.2.2 Data Acquisition and Analysis 109 4.3 Results 112 4.3.1 FHL strongly inhibits SOL, while SOL very weakly inhibits FHL following chronic SCI 114 4.3.2 Inhibitory force feedback interaction between SOL and FHL reorganizes across limbs in cats following chronic LSH 123 4.3.3 Patterns of inhibition between SOL and FHL is similar across cats irrespective of time post chronic SCI 125 4.3.4 FHL strongly inhibits PLT, while PLT very weakly inhibits FHL following chronic SCI 128 4.3.5 Altered pattern of inhibitory force feedback between PLT and FHL is bilateral following chronic LSH irrespective of the side of lesion 137 4.3.6 Inhibition between PLT and FHL is similar across cats following chronic LSH irrespective of the time post SCI 138 4.3.7 Clasp knife inhibition 141 4.4 Discussion 144 CHAPTER: 5 DISCUSSION 148 REFERENCES 167 ix
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