Studies on connective and neurological tissues in relation to disease

The 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.;Process of non-enzymatic glycosylation, i.e. glycation, is rather slow resulting in the formation of sugar-mediated crosslinks, also known as Advanced Glycation Endproducts (AGEs), within the native structure of type I collagen. This process occurs in all animals but is accelerated in diabetics. However, the exact locations or regions of high propensity for the formation of these crosslinks within the packing structure of collagen are largely unknown, despite our knowledge of the underlying chemistry. The results presented in this thesis inform on the location of possible crosslinks to and correlate the effects of crosslinks to the structural and functional sites present on the D-periodic arrangement of collagen into fibrils. Prolonged treatment with iodine, as a wound disinfectant, is detrimental to the structure of collagen underlying the wound site. Diabetic patients are more prone to injuries to limb extremities. Wounded extremities are commonly amputated to prevent the spread of infection to the rest of the body followed by low dose iodine application to the wound site. The results presented in this thesis demonstrate specific disintegration of collagen fibrils in rat tail tendons, from a short iodine treatment.;TBI results in the loss of neurological control and/or function of various parts of the body. 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.