Paranodal structure in diabetic sensory polyneuropathy

Thomas, P. K.; Beamish, N. G.; Small, J. R.; King, R. H. M.; Tesfaye, Solomon; Ward, John D.; Tsigos, Constantine; Young, Robert J.; Boulton, A. J. M.

doi:10.1007/s004010050569

Cited by 30 publications

(23 citation statements)

References 23 publications

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“…Such pathology includes demyelination and a significant loss of myelinated fibres due to axonal degeneration [9,10]. In addition axonal atrophy and axo-glial dysjunction have also been demonstrated in some [31,32] but not in other [20,21,33] studies. Unmyelinated fibres demonstrate both degeneration and regeneration in a variety of clinical syndromes of diabetic neuropathy [10,11,31,34].…”

Section: Discussionmentioning

confidence: 99%

“…Experimental studies demonstrate progressive molecular alterations leading to nodal and paranodal degeneration with axo-glial dysjunction and axonal atrophy [19]. However, these alterations have not been observed in diabetic patients [20,21]. Increasing attention has focused on the Schwann cell, as it is not only responsible for insulating the axon and maintaining axonal calibre but is also vital for effective nerve regeneration [22].…”

Section: Introductionmentioning

confidence: 99%

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Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

et al. 2005

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Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

et al. 2005

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“…Pathological studies of sural nerve biopsies from patients with diabetic neuropathy typically demonstrate axonal atrophy, demyelination, axonal degeneration with regeneration, and microangiopathy (Biessels et al, 2014;Malik et al, 1989Malik et al, , 2005Thomas et al, 1996). We have previously shown that sural nerve endoneurial capillary density was increased and luminal area was decreased in subjects with impaired glucose tolerance (IGT) who progressed to type 2 diabetes (T2DM) (Thrainsdottir, Malik, & Dahlin, 2003).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy

et al. 2017

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Objectives: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagyrelated structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Patients and Methods:Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM.Results: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. Conclusions:We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy. K E Y W O R D Sautophagy, diabetes, endoneurial capillary, impaired glucose tolerance, morphometry, peripheral neuropathy

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“…The low-level pre-and postnatal inorganic Cd exposure affects the bioelectrical and higher order functions of the nervous system (Desi et al, 1998). Although many studies about electrophysiologic and morphologic effects of diabetes and Cd intoxication on nervous system have been realized (Addicks et al, 1993;Agar et al, 1994;Agar et al, 1996;Agar et al, 1999a;Agar et al, 2000a, Agar et al, 2000cApaydin et al, 1993a;Benstead & Sangalang, 1995;Bradley et al, 1990;Desi et al, 1998;Engelstad et al, 1997, Ghani et al, 1999Gulati et al, 1986;Italiano et al, 1993;Jirmanova, 1993;Malik, 1997;Malik et al, 2001;Manca et al, 1991b;Ochodnicka et al, 1995;Ozaki et al, 1996;Sato et al, 1978;Sima, 1994;Thomas et al, 1996;Walker et al, 1999, Yargicoglu et al, 1998Yargicoglu et al, 1999), the effect of diabetes and Cd together on peripheral nervous system morphology has not been previously studied. The purpose of this study was to investigate ultrastructural changes in the peripheral and sciatic nerves, formed by experimental diabetes mellitus and Cd toxicity in rats.…”

Section: Effect Of Cadmium On Sciatic Nerve In Diabetic Rats: An Ultrmentioning

confidence: 96%

Effect of Cadmium on Sciatic Nerve in Diabetic Rats: An Ultrastructural Study

Demır

Akkoyunlu

Ağar

et al. 2002

International Journal of Neuroscience

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The present study demonstrated the ultrastructural effects of diabetes and cadmium on the peripheral nervous system. In this study we used 52 healthy Swiss male albino rats. They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and diabetic and cadmium (D + Cd). The diabetic condition was induced by intravenous injection of 5 mg alloxan/100 g body weight, via the caudal vein. Cd and D + Cd groups were injected with CdCl2 intraperitoneally (2 mg/Kg/week) for two months. At the end of the experimental period, animals were sacrificed and their sciatic nerves were dissected. The tissue samples were investigated by using light and electron microscopic techniques. Upon investigation, it was seen that myelinated axons in sciatic nerve of diabetic and Cd treatment groups had onion-bulb type myelin destruction, melting, and protrusion. Basal lamina of capillary endothelia of D, Cd, and D + Cd groups were thickened and the endothelial apical membrane was rough. In conclusion, Cd toxicity exacerbated the destructive effect of diabetes on the peripheral nervous system.

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Paranodal structure in diabetic sensory polyneuropathy

Cited by 30 publications

References 23 publications

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy

Effect of Cadmium on Sciatic Nerve in Diabetic Rats: An Ultrastructural Study

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