Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445143
Title: Investigation into the mechanisms contributing to impaired neural control of skin blood flow in diabetic rats
Author: Hinder, Lucy Marie
ISNI:       0000 0001 3578 8115
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2007
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Abstract:
Diabetic patients present with initial hypersensitivity within peripheral located skin, followed later by a switch to nocicpetive insensitivity. Loss of nociception coupled with reduced neurovascular responses to injury can result in ulceration, particularly of the foot. One of the neurovascular responses to injury is axon reflex vasodilation of the affected skin, mediated by calcitonin gene-related peptide (CGRP) release from the afferent nerve. A working protocol was established to measure neurogenic vasodilation evoked by short electrical stimulation of the saphenous nerve. In the streptozotocin-induced diabetic rat model, four weeks of untreated diabetes resulted in an approximate 40% reduction in the skin blood flow response, with a further 45% reduction by eight weeks. Vasodilation to acute administration of CGRP was unchanged at four weeks and reduced by approximately 60% by eight weeks. Antioxidant (alpha-lipoic acid) or ACE-inhibitor (lisinopril) treatment prevented the progression of deterioration between four and eight weeks of diabetes, but could not prevent the development of the neurogenic deficit over the first four weeks of the disease. IGF-I replacement therapy not only prevented the deterioration of the neurogenic response between four and eight weeks of diabetes, but it completely normalised the functional deficit to control levels. Diabetic rats also demonstrated tactile allodynia, thermal hyperalgesia and reduced CGRP content of dorsal root ganglion cells, all of which were normalised by IGF-I treatment. The data indicate that an improvement in oxidant status and blood flow may be effective in halting the early progression of diabetic neuropathy and that IGF-I replacement therapy may prove to be efficacious in the alleviation of painful neuropathy and functional hyperaemia in the diabetic foot.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.445143  DOI: Not available
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