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Effect of Cyclooxygenase (COX)-2 Activation on Diabetic Neuropathy

by Kellogg, Aaron

Abstract (Summary)
Diabetic peripheral and autonomic neuropathies are debilitating complications of disease, leading to increased risk of amputation, hyperalgesia and allodynia or hypoalgesia, and increased morbidity and mortality due to myocardial infarctions. We propose that activation of the COX-2 pathway by hyperglycemia with secondary neurovascular deficits are implicated in the pathogenesis of experimental diabetic peripheral sensorymotor and autonomic neuropathies. We further propose that selective COX-2 inhibition may provide a protective effect against the onset and/or progression of these diabetic neuropathies. This hypothesis was tested by the use of a COX-2 gene knockout mouse and a rat model using the selective COX-2 inhibitor celecoxib, using a type 1 diabetes model. Wild-type littermate diabetic mice and untreated diabetic rats developed the normal complications of diabetes such as decreased motor and sensory nerve conduction velocities, increased oxidative stress and inflammation, and alter PG production. Diabetic COX-2 gene knockout mice and rats treated with celecoxib demonstrated protection against deficits in nerve conduction velocity, sensory perception, oxidative stress, and inflammation and maintained normal PG production balance.
Bibliographical Information:

Advisor:

School:University of Toledo Health Science Campus

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:diabetes cyclooxygenase 2 peripheral neuropathy cardiac autonomic

ISBN:

Date of Publication:01/01/2008

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