Skip to main content
Top
Published in: Acta Neuropathologica 4/2012

01-10-2012 | Original Paper

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

Authors: Joshua A. Gregory, Corinne G. Jolivalt, Jared Goor, Andrew P. Mizisin, Nigel A. Calcutt

Published in: Acta Neuropathologica | Issue 4/2012

Login to get access

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.
Literature
1.
go back to reference Behse F, Buchthal (1978) Sensory action potentials and biopsy of the sural nerve in neuropathy. Brain 101(3):473–493 Behse F, Buchthal (1978) Sensory action potentials and biopsy of the sural nerve in neuropathy. Brain 101(3):473–493
2.
go back to reference Behse F, Buchthal F, Carlsen F (1977) Nerve biopsy and conduction studies in diabetic neuropathy. J Neurol Neurosurg Psychiatry 40(11):1072–1082PubMedCrossRef Behse F, Buchthal F, Carlsen F (1977) Nerve biopsy and conduction studies in diabetic neuropathy. J Neurol Neurosurg Psychiatry 40(11):1072–1082PubMedCrossRef
3.
go back to reference Beiswenger KK, Calcutt NA, Mizisin AP (2008) Dissociation of thermal hypoalgesia and epidermal denervation in streptozotocin-diabetic mice. Neurosci Lett 442(3):267–272PubMedCrossRef Beiswenger KK, Calcutt NA, Mizisin AP (2008) Dissociation of thermal hypoalgesia and epidermal denervation in streptozotocin-diabetic mice. Neurosci Lett 442(3):267–272PubMedCrossRef
4.
go back to reference Beiswenger KK, Calcutt NA, Mizisin AP (2008) Epidermal nerve fiber quantification in the assessment of diabetic neuropathy. Acta Histochem 110(5):351–362PubMedCrossRef Beiswenger KK, Calcutt NA, Mizisin AP (2008) Epidermal nerve fiber quantification in the assessment of diabetic neuropathy. Acta Histochem 110(5):351–362PubMedCrossRef
5.
go back to reference Bensfield AC, Evans J, Pesayco JP, Mizisin AP, Shelton GD (2011) Recurrent demyelination and remyelination in 37 young bengal cats with polyneuropathy. J Vet Intern Med 25(4):882–889PubMedCrossRef Bensfield AC, Evans J, Pesayco JP, Mizisin AP, Shelton GD (2011) Recurrent demyelination and remyelination in 37 young bengal cats with polyneuropathy. J Vet Intern Med 25(4):882–889PubMedCrossRef
6.
go back to reference Bianchi R, Buyukakilli B, Brines M, Savino C, Cavaletti G, Oggioni N, Lauria G, Borgna M, Lombardi R, Cimen B, Comelekoglu U, Kanik A, Tataroglu C, Cerami A, Ghezzi P (2004) Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proc Natl Acad Sci USA 101(3):823–828PubMedCrossRef Bianchi R, Buyukakilli B, Brines M, Savino C, Cavaletti G, Oggioni N, Lauria G, Borgna M, Lombardi R, Cimen B, Comelekoglu U, Kanik A, Tataroglu C, Cerami A, Ghezzi P (2004) Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proc Natl Acad Sci USA 101(3):823–828PubMedCrossRef
7.
go back to reference Britland ST, Sharma AK, Duguid IG, Thomas PK (1985) Ultrastructural observations on myelinated fibres in the tibial nerve of streptozotocin-diabetic rats: effect of insulin treatment. Life Support Syst 3(Suppl 1):524–529PubMed Britland ST, Sharma AK, Duguid IG, Thomas PK (1985) Ultrastructural observations on myelinated fibres in the tibial nerve of streptozotocin-diabetic rats: effect of insulin treatment. Life Support Syst 3(Suppl 1):524–529PubMed
8.
go back to reference Calcutt NA (2004) Modeling diabetic sensory neuropathy in rats. Methods Mol Med 99:55–65PubMed Calcutt NA (2004) Modeling diabetic sensory neuropathy in rats. Methods Mol Med 99:55–65PubMed
9.
go back to reference Calcutt NA, Campana WM, Eskeland NL, Mohiuddin L, Dines KC, Mizisin AP, O’Brien JS (1999) Prosaposin gene expression and the efficacy of a prosaposin-derived peptide in preventing structural and functional disorders of peripheral nerve in diabetic rats. J Neuropathol Exp Neurol 58(6):628–636PubMedCrossRef Calcutt NA, Campana WM, Eskeland NL, Mohiuddin L, Dines KC, Mizisin AP, O’Brien JS (1999) Prosaposin gene expression and the efficacy of a prosaposin-derived peptide in preventing structural and functional disorders of peripheral nerve in diabetic rats. J Neuropathol Exp Neurol 58(6):628–636PubMedCrossRef
10.
go back to reference Calcutt NA, Freshwater JD, Mizisin AP (2004) Prevention of sensory disorders in diabetic Sprague–Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor. Diabetologia 47(4):718–724PubMedCrossRef Calcutt NA, Freshwater JD, Mizisin AP (2004) Prevention of sensory disorders in diabetic Sprague–Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor. Diabetologia 47(4):718–724PubMedCrossRef
11.
go back to reference Calcutt NA, Mizisin AP, Kalichman MW (1994) Aldose reductase inhibition, Doppler flux and conduction in diabetic rat nerve. Eur J Pharmacol 251(1):27–33PubMedCrossRef Calcutt NA, Mizisin AP, Kalichman MW (1994) Aldose reductase inhibition, Doppler flux and conduction in diabetic rat nerve. Eur J Pharmacol 251(1):27–33PubMedCrossRef
12.
go back to reference Calcutt NA, Muir D, Powell HC, Mizisin AP (1992) Reduced ciliary neuronotrophic factor-like activity in nerves from diabetic or galactose-fed rats. Brain Res 575(2):320–324PubMedCrossRef Calcutt NA, Muir D, Powell HC, Mizisin AP (1992) Reduced ciliary neuronotrophic factor-like activity in nerves from diabetic or galactose-fed rats. Brain Res 575(2):320–324PubMedCrossRef
13.
go back to reference Cameron NE, Cotter MA, Low PA (1991) Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 261(1 Pt 1):E1–E8PubMed Cameron NE, Cotter MA, Low PA (1991) Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 261(1 Pt 1):E1–E8PubMed
14.
go back to reference Cameron NE, Jack AM, Cotter MA (2001) Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats. Free Radic Biol Med 31(1):125–135PubMedCrossRef Cameron NE, Jack AM, Cotter MA (2001) Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats. Free Radic Biol Med 31(1):125–135PubMedCrossRef
15.
go back to reference Cermenati G, Abbiati F, Cermenati S, Brioschi E, Volonterio A, Cavaletti G, Saez E, De Fabiani E, Crestani M, Garcia-Segura LM, Melcangi RC, Caruso D, Mitro N (2012) Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation. J Lipid Res 53(2):300–310PubMedCrossRef Cermenati G, Abbiati F, Cermenati S, Brioschi E, Volonterio A, Cavaletti G, Saez E, De Fabiani E, Crestani M, Garcia-Segura LM, Melcangi RC, Caruso D, Mitro N (2012) Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation. J Lipid Res 53(2):300–310PubMedCrossRef
16.
go back to reference Conti AM, Malosio ML, Scarpini E, Di Giulio AM, Scarlato G, Mantegazza P, Gorio A (1993) Myelin protein transcripts increase in experimental diabetic neuropathy. Neurosci Lett 161(2):203–206PubMedCrossRef Conti AM, Malosio ML, Scarpini E, Di Giulio AM, Scarlato G, Mantegazza P, Gorio A (1993) Myelin protein transcripts increase in experimental diabetic neuropathy. Neurosci Lett 161(2):203–206PubMedCrossRef
17.
go back to reference Conti AM, Scarpini E, Malosio ML, Di Giulio AM, Baron P, Scarlato G, Mantegazza P, Gorio A (1996) In situ hybridization study of myelin protein mRNA in rats with an experimental diabetic neuropathy. Neurosci Lett 207(1):65–69PubMedCrossRef Conti AM, Scarpini E, Malosio ML, Di Giulio AM, Baron P, Scarlato G, Mantegazza P, Gorio A (1996) In situ hybridization study of myelin protein mRNA in rats with an experimental diabetic neuropathy. Neurosci Lett 207(1):65–69PubMedCrossRef
18.
go back to reference Cooper ME, Allen TJ, Jerums G, Doyle AE (1986) Accelerated progression of diabetic nephropathy in the spontaneously hypertensive streptozotocin diabetic rat. Clin Exp Pharmacol Physiol 13(9):655–662PubMedCrossRef Cooper ME, Allen TJ, Jerums G, Doyle AE (1986) Accelerated progression of diabetic nephropathy in the spontaneously hypertensive streptozotocin diabetic rat. Clin Exp Pharmacol Physiol 13(9):655–662PubMedCrossRef
19.
20.
21.
go back to reference Edwards L, Ring C, McIntyre D, Winer JB, Martin U (2008) Cutaneous sensibility and peripheral nerve function in patients with unmedicated essential hypertension. Psychophysiology 45(1):141–147PubMed Edwards L, Ring C, McIntyre D, Winer JB, Martin U (2008) Cutaneous sensibility and peripheral nerve function in patients with unmedicated essential hypertension. Psychophysiology 45(1):141–147PubMed
22.
go back to reference Elliott J, Tesfaye S, Chaturvedi N, Gandhi RA, Stevens LK, Emery C, Fuller JH (2009) Large-fiber dysfunction in diabetic peripheral neuropathy is predicted by cardiovascular risk factors. Diabetes Care 32(10):1896–1900PubMedCrossRef Elliott J, Tesfaye S, Chaturvedi N, Gandhi RA, Stevens LK, Emery C, Fuller JH (2009) Large-fiber dysfunction in diabetic peripheral neuropathy is predicted by cardiovascular risk factors. Diabetes Care 32(10):1896–1900PubMedCrossRef
23.
go back to reference Forrest KY, Maser RE, Pambianco G, Becker DJ, Orchard TJ (1997) Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes 46(4):665–670PubMedCrossRef Forrest KY, Maser RE, Pambianco G, Becker DJ, Orchard TJ (1997) Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes 46(4):665–670PubMedCrossRef
24.
go back to reference Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab 28(12):1877–1891PubMedCrossRef Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab 28(12):1877–1891PubMedCrossRef
25.
go back to reference Hall SM (1983) The response of the (myelinating) Schwann cell population to multiple episodes of demyelination. J Neurocytol 12(1):1–12PubMedCrossRef Hall SM (1983) The response of the (myelinating) Schwann cell population to multiple episodes of demyelination. J Neurocytol 12(1):1–12PubMedCrossRef
26.
go back to reference Harris M, Eastman R, Cowie C (1993) Symptoms of sensory neuropathy in adults with NIDDM in the US population. Diabetes Care 16(11):1446–1452PubMedCrossRef Harris M, Eastman R, Cowie C (1993) Symptoms of sensory neuropathy in adults with NIDDM in the US population. Diabetes Care 16(11):1446–1452PubMedCrossRef
27.
go back to reference Hendley ED, Cierpial MA, McCarty R (1988) Sympathetic-adrenal medullary response to stress in hyperactive and hypertensive rats. Physiol Behav 44(1):47–51PubMedCrossRef Hendley ED, Cierpial MA, McCarty R (1988) Sympathetic-adrenal medullary response to stress in hyperactive and hypertensive rats. Physiol Behav 44(1):47–51PubMedCrossRef
28.
go back to reference Jakobsen J (1976) Axonal dwindling in early experimental diabetes. I. A study of cross sectioned nerves. Diabetologia 12(6):539–546PubMedCrossRef Jakobsen J (1976) Axonal dwindling in early experimental diabetes. I. A study of cross sectioned nerves. Diabetologia 12(6):539–546PubMedCrossRef
29.
go back to reference Jarmuzewska EA, Ghidoni A, Mangoni AA (2007) Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes. Eur Neurol 57(2):91–95PubMedCrossRef Jarmuzewska EA, Ghidoni A, Mangoni AA (2007) Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes. Eur Neurol 57(2):91–95PubMedCrossRef
30.
go back to reference Kalichman MW, Powell HC, Mizisin AP (1998) Reactive, degenerative, and proliferative Schwann cell responses in experimental galactose and human diabetic neuropathy. Acta Neuropathol 95(1):47–56PubMedCrossRef Kalichman MW, Powell HC, Mizisin AP (1998) Reactive, degenerative, and proliferative Schwann cell responses in experimental galactose and human diabetic neuropathy. Acta Neuropathol 95(1):47–56PubMedCrossRef
31.
go back to reference Kamiya H, Murakawa Y, Zhang W, Sima AAF (2005) Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes. Diabetes Metab Res Rev 21(5):448–458PubMedCrossRef Kamiya H, Murakawa Y, Zhang W, Sima AAF (2005) Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes. Diabetes Metab Res Rev 21(5):448–458PubMedCrossRef
32.
go back to reference Kawashima R, Kojima H, Nakamura K, Arahata A, Fujita Y, Tokuyama Y, Saito T, Furudate S-I, Kurihara T, Yagishita S, Kitamura K, Tamai Y (2007) Alterations in mRNA expression of myelin proteins in the sciatic nerves and brains of streptozotocin-induced diabetic rats. Neurochem Res 32(6):1002–1010PubMedCrossRef Kawashima R, Kojima H, Nakamura K, Arahata A, Fujita Y, Tokuyama Y, Saito T, Furudate S-I, Kurihara T, Yagishita S, Kitamura K, Tamai Y (2007) Alterations in mRNA expression of myelin proteins in the sciatic nerves and brains of streptozotocin-induced diabetic rats. Neurochem Res 32(6):1002–1010PubMedCrossRef
33.
go back to reference Kennedy JM, Zochodne DW (2005) Experimental diabetic neuropathy with spontaneous recovery: is there irreparable damage? Diabetes 54(3):830–837PubMedCrossRef Kennedy JM, Zochodne DW (2005) Experimental diabetic neuropathy with spontaneous recovery: is there irreparable damage? Diabetes 54(3):830–837PubMedCrossRef
34.
go back to reference Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47(4):1042–1048PubMedCrossRef Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47(4):1042–1048PubMedCrossRef
35.
go back to reference Koistinaho J, Wadhwani KC, Rapoport SI (1989) Increased density of perivascular adrenergic innervation in tibial and vagus nerves of spontaneously hypertensive rats. J Neurosci Res 24(3):424–430PubMedCrossRef Koistinaho J, Wadhwani KC, Rapoport SI (1989) Increased density of perivascular adrenergic innervation in tibial and vagus nerves of spontaneously hypertensive rats. J Neurosci Res 24(3):424–430PubMedCrossRef
36.
go back to reference Kursula P (2008) Structural properties of proteins specific to the myelin sheath. Amino Acids 34(2):175–185PubMedCrossRef Kursula P (2008) Structural properties of proteins specific to the myelin sheath. Amino Acids 34(2):175–185PubMedCrossRef
37.
go back to reference Malmberg AB, Mizisin AP, Calcutt NA, von Stein T, Robbins WR, Bley KR (2004) Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch. Pain 111(3):360–367PubMedCrossRef Malmberg AB, Mizisin AP, Calcutt NA, von Stein T, Robbins WR, Bley KR (2004) Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch. Pain 111(3):360–367PubMedCrossRef
38.
go back to reference Maser RE, Steenkiste AR, Dorman JS, Nielsen VK, Bass EB, Manjoo Q, Drash AL, Becker DJ, Kuller LH, Greene DA (1989) Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes 38(11):1456–1461PubMedCrossRef Maser RE, Steenkiste AR, Dorman JS, Nielsen VK, Bass EB, Manjoo Q, Drash AL, Becker DJ, Kuller LH, Greene DA (1989) Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes 38(11):1456–1461PubMedCrossRef
39.
go back to reference Mizisin AP, Calcutt NA, DiStefano PS, Acheson A, Longo FM (1997) Aldose reductase inhibition increases CNTF-like bioactivity and protein in sciatic nerves from galactose-fed and normal rats. Diabetes 46(4):647–652PubMedCrossRef Mizisin AP, Calcutt NA, DiStefano PS, Acheson A, Longo FM (1997) Aldose reductase inhibition increases CNTF-like bioactivity and protein in sciatic nerves from galactose-fed and normal rats. Diabetes 46(4):647–652PubMedCrossRef
40.
go back to reference Mizisin AP, Nelson RW, Sturges BK, Vernau KM, Lecouteur RA, Williams DC, Burgers ML, Shelton GD (2007) Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol 113(4):431–442PubMedCrossRef Mizisin AP, Nelson RW, Sturges BK, Vernau KM, Lecouteur RA, Williams DC, Burgers ML, Shelton GD (2007) Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol 113(4):431–442PubMedCrossRef
41.
go back to reference Mizisin AP, Powell HC (1993) Schwann cell injury is attenuated by aldose reductase inhibition in galactose intoxication. J Neuropathol Exp Neurol 52(1):78–86PubMedCrossRef Mizisin AP, Powell HC (1993) Schwann cell injury is attenuated by aldose reductase inhibition in galactose intoxication. J Neuropathol Exp Neurol 52(1):78–86PubMedCrossRef
42.
go back to reference Paton JFR, Waki H (2009) Is neurogenic hypertension related to vascular inflammation of the brainstem? Neurosci Biobehav Rev 33(2):89–94PubMedCrossRef Paton JFR, Waki H (2009) Is neurogenic hypertension related to vascular inflammation of the brainstem? Neurosci Biobehav Rev 33(2):89–94PubMedCrossRef
43.
go back to reference Pirart J (1977) Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (author’s transl). Diabetes Metab 3(2):97–107 Pirart J (1977) Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (author’s transl). Diabetes Metab 3(2):97–107
44.
go back to reference Pop-Busui R, Herman WH, Feldman EL, Low PA, Martin CL, Cleary PA, Waberski BH, Lachin JM, Albers JW (2010) DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history. Curr Diab Rep 10(4):276–282PubMedCrossRef Pop-Busui R, Herman WH, Feldman EL, Low PA, Martin CL, Cleary PA, Waberski BH, Lachin JM, Albers JW (2010) DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history. Curr Diab Rep 10(4):276–282PubMedCrossRef
45.
go back to reference Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, Marshall A, Boulton AJM, Efron N, Malik RA (2007) Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes 56(8):2148–2154PubMedCrossRef Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, Marshall A, Boulton AJM, Efron N, Malik RA (2007) Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes 56(8):2148–2154PubMedCrossRef
46.
go back to reference Sabbatini M, Bellagamba G, Vega JA, Amenta F (2001) Effect of antihypertensive treatment on peripheral nerve vasculature in spontaneously hypertensive rats. Clin Exp Hypertens 23(1–2):157–166PubMedCrossRef Sabbatini M, Bellagamba G, Vega JA, Amenta F (2001) Effect of antihypertensive treatment on peripheral nerve vasculature in spontaneously hypertensive rats. Clin Exp Hypertens 23(1–2):157–166PubMedCrossRef
47.
go back to reference Sabbatini M, Vega JA, Amenta F (1996) Peripheral nerve vascular changes in spontaneously hypertensive rats. Neurosci Lett 217(2–3):85–88PubMedCrossRef Sabbatini M, Vega JA, Amenta F (1996) Peripheral nerve vascular changes in spontaneously hypertensive rats. Neurosci Lett 217(2–3):85–88PubMedCrossRef
48.
go back to reference Sharma AK, Thomas PK (1974) Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 23(1):1–15PubMedCrossRef Sharma AK, Thomas PK (1974) Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 23(1):1–15PubMedCrossRef
49.
go back to reference Sima AA, Zhang W, Xu G, Sugimoto K, Guberski D, Yorek MA (2000) A comparison of diabetic polyneuropathy in type II diabetic BBZDR/Wor rats and in type I diabetic BB/Wor rats. Diabetologia 43(6):786–793PubMedCrossRef Sima AA, Zhang W, Xu G, Sugimoto K, Guberski D, Yorek MA (2000) A comparison of diabetic polyneuropathy in type II diabetic BBZDR/Wor rats and in type I diabetic BB/Wor rats. Diabetologia 43(6):786–793PubMedCrossRef
50.
go back to reference Smith KJ, Blakemore WF, Murray JA, Patterson RC (1982) Internodal myelin volume and axon surface area. A relationship determining myelin thickness? J Neurol Sci 55(2):231–246PubMedCrossRef Smith KJ, Blakemore WF, Murray JA, Patterson RC (1982) Internodal myelin volume and axon surface area. A relationship determining myelin thickness? J Neurol Sci 55(2):231–246PubMedCrossRef
51.
go back to reference Somani P, Singh HP, Saini RK, Rabinovitch A (1979) Streptozotocin-induced diabetes in the spontaneously hypertensive rat. Metabolism 28(11):1075–1077PubMedCrossRef Somani P, Singh HP, Saini RK, Rabinovitch A (1979) Streptozotocin-induced diabetes in the spontaneously hypertensive rat. Metabolism 28(11):1075–1077PubMedCrossRef
52.
go back to reference Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33(10):2285–2293PubMedCrossRef Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33(10):2285–2293PubMedCrossRef
53.
go back to reference Tesfaye S, Chaturvedi N, Eaton SEM, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH (2005) Vascular risk factors and diabetic neuropathy. N Engl J Med 352(4):341–350PubMedCrossRef Tesfaye S, Chaturvedi N, Eaton SEM, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH (2005) Vascular risk factors and diabetic neuropathy. N Engl J Med 352(4):341–350PubMedCrossRef
54.
go back to reference Tomassoni D, Traini E, Vitaioli L, Amenta F (2004) Morphological and conduction changes in the sciatic nerve of spontaneously hypertensive rats. Neurosci Lett 362(2):131–135PubMedCrossRef Tomassoni D, Traini E, Vitaioli L, Amenta F (2004) Morphological and conduction changes in the sciatic nerve of spontaneously hypertensive rats. Neurosci Lett 362(2):131–135PubMedCrossRef
56.
go back to reference Tomlinson KC, Gardiner SM, Bennett T (1990) Blood pressure in streptozotocin-treated Brattleboro and Long-Evans rats. Am J Physiol 258(4 Pt 2):R852–R859PubMed Tomlinson KC, Gardiner SM, Bennett T (1990) Blood pressure in streptozotocin-treated Brattleboro and Long-Evans rats. Am J Physiol 258(4 Pt 2):R852–R859PubMed
57.
go back to reference Tsutsu N, Takata Y, Nunoi K, Kikuchi M, Takishita S, Sadoshima S, Fujishima M (1989) Glucose tolerance and insulin secretion in conscious and unrestrained normotensive and spontaneously hypertensive rats. Metabolism 38(1):63–66PubMedCrossRef Tsutsu N, Takata Y, Nunoi K, Kikuchi M, Takishita S, Sadoshima S, Fujishima M (1989) Glucose tolerance and insulin secretion in conscious and unrestrained normotensive and spontaneously hypertensive rats. Metabolism 38(1):63–66PubMedCrossRef
58.
go back to reference Tuck RR, Schmelzer JD, Low PA (1984) Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy. Brain 107:935–950PubMedCrossRef Tuck RR, Schmelzer JD, Low PA (1984) Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy. Brain 107:935–950PubMedCrossRef
59.
go back to reference Walker D, Carrington A, Cannan SA, Sawicki D, Sredy J, Boulton AJ, Malik RA (1999) Structural abnormalities do not explain the early functional abnormalities in the peripheral nerves of the streptozotocin diabetic rat. J Anat 195(Pt 3):419–427PubMedCrossRef Walker D, Carrington A, Cannan SA, Sawicki D, Sredy J, Boulton AJ, Malik RA (1999) Structural abnormalities do not explain the early functional abnormalities in the peripheral nerves of the streptozotocin diabetic rat. J Anat 195(Pt 3):419–427PubMedCrossRef
60.
go back to reference Xu XJ, Plesan A, Yu W, Hao JX, Wiesenfeld-Hallin Z (2001) Possible impact of genetic differences on the development of neuropathic pain-like behaviors after unilateral sciatic nerve ischemic injury in rats. Pain 89(2–3):135–145PubMedCrossRef Xu XJ, Plesan A, Yu W, Hao JX, Wiesenfeld-Hallin Z (2001) Possible impact of genetic differences on the development of neuropathic pain-like behaviors after unilateral sciatic nerve ischemic injury in rats. Pain 89(2–3):135–145PubMedCrossRef
61.
go back to reference Zhu Y-L, Xie Z-L, Wu Y-W, Duan W-R, Xie Y-K (2012) Early demyelination of primary A-fibers induces as rapid onset of neuropathic pain in rat. Neuroscience 200:186–198PubMedCrossRef Zhu Y-L, Xie Z-L, Wu Y-W, Duan W-R, Xie Y-K (2012) Early demyelination of primary A-fibers induces as rapid onset of neuropathic pain in rat. Neuroscience 200:186–198PubMedCrossRef
Metadata
Title
Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats
Authors
Joshua A. Gregory
Corinne G. Jolivalt
Jared Goor
Andrew P. Mizisin
Nigel A. Calcutt
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 4/2012
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-012-1012-6

Other articles of this Issue 4/2012

Acta Neuropathologica 4/2012 Go to the issue