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STUDIES ON CONNECTIVE AND NEUROLOGICAL TISSUES IN RELATION TO DISEASE
Title
STUDIES ON CONNECTIVE AND NEUROLOGICAL TISSUES IN RELATION TO DISEASE
Creator
Madhurapantula, Rama Sashank
Date
2015, 2015-12
Description
The structure of connective tissue is of great importance for homeostasis of the cells present within it. Pathologies leading to changes in...
Show moreThe structure of connective tissue is of great importance for homeostasis of the cells present within it. Pathologies leading to changes in the structure of the extracellular matrix (ECM), in particular collagen have been shown to play a pivotal role in the progression of various diseases. Similarly, changes in the structure of specific elements in neurological tissues, such as myelin, have been shown to elicit adverse responses to injury. This thesis explores two main aspects: 1) the structural changes brought about by high sugar concentrations, much similar to that found in diabetic patients, to the structure of type I collagen and 2) possible effects of traumatic brain injury (TBI) to the structure of neurons in rat brains. Specific changes in the structure and packing of collagens in various tissues could be potential therapeutic targets to control the progression of related diseases. However, the information available on the nature, specificity and the relevance of these changes at a molecular level are largely unknown and have been explored only sparsely. The result of non-enzymatic glycosylation i.e. glycation, is the formation of sugar- mediated crosslinks within the native structure of type I collagen. The chemistry behind these crosslinks, also known as Advanced Glycation Endproducts (AGEs), has been known for decades. However, the exact locations or regions of high propensity for the formation of these crosslinks within the packing structure of collagen are largely unknown. The results presented in this thesis inform on the location of possible crosslinks using the principle of Multiple Isomorphic Replacement (MIR) to and correlate the effects of crosslinks to the structural and functional sites present on the D-periodic arrangement of collagen into fibrils. An extension to this is the study of the effects of povidone-iodine on the packing structure of collagen. Iodine is used as a common disinfectant in surgery and first aid. Prolonged treatment with iodine is detrimental to the structure of collagen underlying the wound site (surgical or otherwise). This is particularly important in large surface area wounds, as seen in open-heart, hip and joint replacement surgeries and amputations. Diabetic patients are more prone to injuries to limb extremities and a common procedure to stop infections from spreading to the rest of the body is amputation of the limb and constant treatment with low doses of iodine immediately following surgery for a certain length of time. The results presented in this thesis demonstrate specific disintegration of collagen fibrils in rat tail tendons, from a short iodine treatment. This is detrimental for cellular activity, more so in processes like wound healing. TBI results in the loss of neurological control and/or function of various parts of the body, governed by this region. The results presented herein, inform and support the finding that neuroplasticity, in the hemisphere opposite to that where injury was delivered, compensates for the functional deficits as a result of TBI. The data presented here can be used in developing rehabilitation regimens for TBI patients on case-to-case basis to restore most of the functional deficits observed thereof, and also as a factor of predicting the onset of secondary neurological disorders (for instance amyloid related pathologies) at a later stage in life.
Ph.D. in Biology, December 2015
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