Increased susceptibility to ischemia and macrophage activation in STZ-diabetic rat nerve

Nukada, Hitoshi; McMorran, P. Denise; Baba, Masayuki; Ogasawara, Saori; Yagihashi, Soroku

doi:10.1016/j.brainres.2010.11.084

Cited by 27 publications

(14 citation statements)

References 51 publications

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“…Numerous publications of both our group [55–58] and others [59–67] suggest that ROS and peroxynitrite play a key role in nerve conduction slowing, neurovascular dysfunction, changes in behavioral measures of sensory function, and morphological manifestations of diabetic peripheral neuropathy. Furthermore, oxidative-nitrosative stress leads to formation of advanced glycation end products and proinflammatory response, two other major contributors to neuropathic changes in diabetes [68–72] and, potentially, prediabetes [73]. Interestingly and surprisingly, enhanced peripheral nerve oxidative-nitrosative stress was associated with SNCV, but not MNCV, deficit in 20 wk-old Zucker fa/fa rats.…”

Section: Discussionmentioning

confidence: 99%

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress

Lupachyk

Watcho

Hasanova

et al. 2012

Free Radical Biology and Medicine

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Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome, prior to overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased NEFA, and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. 16 wk-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA, displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mgkg−1d−1, 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit, changes in behavioral measures of sensory function, and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find use in management of this condition.

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Section: Discussionmentioning

confidence: 99%

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress

Lupachyk

Watcho

Hasanova

et al. 2012

Free Radical Biology and Medicine

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“…Macrophage infiltration and proliferation have been observed in nerves from mouse models of diabetes 97,98 , and upregulation of proinflammatory genes during activation of inflammatory pathways in the PNS [99][100][101] further implicates involvement of RAGE-mediated Schwann cell involvement in the inflammatory response. One up regulated gene encodes the S100 calcium binding protein A8/A9 (REF.…”

Section: Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 94%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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“…Significant increases Nukada et al, 2000. In reperfusion nerve injury, the density of Iba-1 positive endoneurial macrophages was significantly greater in STZ-diabetic nerve than in control nerves (Nukada et al, 2011). In reperfusion nerve injury, the density of Iba-1 positive endoneurial macrophages was significantly greater in STZ-diabetic nerve than in control nerves (Nukada et al, 2011).…”

Section: Physiologic and Morphologic Vulnerability To Reperfusion Nermentioning

confidence: 95%

Ischemia and diabetic neuropathy

Nukada

2014

Handbook of Clinical Neurology

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Increased susceptibility to ischemia and macrophage activation in STZ-diabetic rat nerve

Cited by 27 publications

References 51 publications

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Ischemia and diabetic neuropathy

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