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Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats

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Abstract

Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behavioral, physiological and structural indices of neuropathy were measured for up to 6 months in spontaneously hypertensive and age-matched normotensive rats with or without concurrent streptozotocin-induced diabetes. Hypertensive rats developed nerve ischemia, thermal hyperalgesia, nerve conduction slowing and axonal atrophy. Thinly myelinated fibers with supernumerary Schwann cells indicative of cycles of demyelination and remyelination were also identified along with reduced nerve levels of myelin basic protein. Similar disorders were noted in streptozotocin-diabetic rats, except that thinly myelinated fibers were not observed and expression of myelin basic protein was normal. Superimposing diabetes on hypertension compounded disorders of nerve blood flow, conduction slowing and axonal atrophy and increased the incidence of thinly myelinated fibers. Rats with combined insulinopenia, hyperglycemia and hypertension provide a model for diabetic neuropathy that offers an opportunity to study mechanisms of Schwann cell pathology and suggests that hypertension may contribute to the etiology of diabetic neuropathy.

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Acknowledgments

Our thanks to Dr. Debbie Chen, Mr. Victor Arballo and Ms. Sandra Myskowski for technical assistance. Supported by NIH grant DK-057629 (NAC) and JDRF Career Development Award (CGJ). The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0612, USA

    Joshua A. Gregory, Corinne G. Jolivalt, Andrew P. Mizisin & Nigel A. Calcutt

  2. Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093-0612, USA

    Jared Goor

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  1. Joshua A. Gregory
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Correspondence to Nigel A. Calcutt.

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Gregory, J.A., Jolivalt, C.G., Goor, J. et al. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats. Acta Neuropathol 124, 561–573 (2012). https://doi.org/10.1007/s00401-012-1012-6

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  • DOI: https://doi.org/10.1007/s00401-012-1012-6

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