Sural nerve oxygen tension in diabetes.

Newrick, P. G.; Wilson, Andrew J.; Jakubowski, Jan; Boulton, A. J. M.; Ward, John D.

doi:10.1136/bmj.293.6554.1053

Cited by 246 publications

(123 citation statements)

References 7 publications

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“…Additionally, we also demonstrate a reduction in luminal size which has not been demonstrated previously, though these studies were performed in patients with mild and established neuropathy [12][13][14]. This is important as it provides a morphological basis for an early reduction in nerve blood flow and endoneurial oxygenation [7].…”

Section: Discussionsupporting

confidence: 73%

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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: Discussionsupporting

confidence: 73%

“…Metabolic [3] and vascular [4][5][6][7] factors play an important role in its pathogenesis. Detailed neurophysiological studies in diabetic patients have shown that demyelination precedes axonal loss and that the latter may be responsible for the symptoms [8].…”

Section: Introductionmentioning

confidence: 99%

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

et al. 2005

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“…Similar subclinical functional indicators are found in newly-diagnosed diabetic patients [5,6]. Endoneurial hypoxia and reduced blood flow are also present in patients with established neuropathy [7][8][9]; therefore it is likely that neurovascular effects play a major role in the aetiology of this diabetic complication.…”

supporting

confidence: 56%

“…Sciatic nerve endoneurium is hypoxic in experimental diabetes [1,36,39], as is the sural nerve in neuropathic patients [7]. This provides one potential stimulus for endothelial ET synthesis and release [27].…”

Section: Discussionmentioning

confidence: 99%

The potential contribution of endothelin-1 to neurovascular abnormalities in streptozotocin-diabetic rats

1994

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Summary Abnormal vascular endothelium function may contribute to the reduced nerve perfusion implicated in the aetiology of neuropathy in diabetes mellitus. The aim was to test the hypothesis that a powerful vasoconstrictor, endothelin-1, could be involved in nerve dysfunction in streptozotocin-diabetic rats. After 6 weeks of untreated diabetes, rats were implanted with osmotic minipumps which continuously delivered the endothelin-1 antagonist, BQ-123, to the circulation via a jugular vein cannula. Sciatic motor conduction velocity, monitored serially, was increased after 4 days, treatment (p = 0.028), and reached asymptote by 9-11 days (p = 0.0001), when the degree of amelioration was approximately 60 % of the initial diabetic deficit. Treatment of non-diabetic rats for 13 days with BQ-123 had no significant effect on motor conduction velocity. Sensory saphenous nerve conduction velocity was measured acutely after 20 days, BQ-123 treatment. The amelioration of a sensory deficit was approximately 80 % (p < 0.001); the resultant conduction velocity value was not significantly different from that of a non-diabetic control group. After 20 days, treatment, sciatic nutritive endoneurial blood flow was measured by microelectrode polarography and hydrogen clearance. A 48 % deficit with untreated diabetes (p < 0.001) was 64 % ameliorated by BQ-123 treatment (p < 0.001). In non-diabetic rats, BQ-123 treatment had no effect on blood flow. We conclude that endothelin-1 does not seem to be involved in the control of nerve blood flow in non-diabetic rats; however, it makes a major contribution to the perfusion deficit in experimental diabetes. This has deleterious consequences for nerve conduction, and it is possible that endothelin-1 receptor blockade may have therapeutic potential in diabetic patients. [Diabetologia (1994[Diabetologia ( ) 37: 1209[Diabetologia ( -1215

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“…these are not fully known in detail. A plausible (but arguable) current view is that vascular dysfunction, which causes decreased nerve blood flow and results in endoneurial hypoxia sufficient to damage nerve fibres (Newrick et al, 1986;Low et al, 1987;Cameron et al, 1991b;Tesfaye et al, 1992), provides the most important contribution to the aetiology of diabetic neuropathy.…”

Section: Introductionmentioning

confidence: 99%

The effects of evening primrose oil on nerve function and capillarization in streptozotocin‐diabetic rats: modulation by the cyclo‐oxygenase inhibitor flurbiprofen

Cameron

Cotter

Dines

et al. 1993

British J Pharmacology

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1 The aims of this study were first, to examine whether deficits in nerve conduction in streptozotocindiabetic rats could be reversed by a 10% dietary supplement of evening primrose oil. Second, to determine the time-course of reversal, and third, to assess whether the effects could be blocked by the cylco-oxygenase inhibitor flurbiprofen (5 mg kg-' day-1).2 One-month diabetes produced 20% and 15% deficits in sciatic motor and saphenous sensory conduction velocity respectively, which were maintained over 2 months diabetes. 3 The effect of 1-month evening primrose oil treatment on abnormalities caused by an initial month of untreated diabetes was examined. Motor and sensory nerve conduction velocity were restored to the non-diabetic level. 4 Resistance to hypoxic conduction failure was investigated for sciatic nerve trunk in vitro. The 80% conduction failure times were 29% and 55% prolonged by 1-and 2-month diabetes respectively. Evening primrose oil did not reverse the increased hypoxic resistance following 1-month untreated diabetes. 5 Sciatic nerve endoneurial capillary density was not significantly affected by diabetes, but was 16% increased in diabetic rats with reversal by evening primrose oil treatment for 1 month compared to 2-month untreated diabetes. 6 Serial motor conduction velocity measurement after 3-month untreated diabetes revealed complete normalization by evening primrose oil within 4 days. Cessation of treatment resulted in a rapid decline in conduction velocity over 24 h. 7 In a preventive study of 2-month duration, 6 groups of rats were used. These comprised non-diabetic controls, diabetic rats, and evening primrose oil-treated diabetic rats, both with and without flurbiprofen treatment. Flurbiprofen had no significant effect in non-diabetic rats, but produced an 11% worsening of motor conduction velocity and a 21% reduction of sciatic capillary density in diabetic rats. Evening primrose oil prevented the decreases in conduction velocity and increased hypoxic resistance with diabetes, and caused a 23% increase in capillary density. Flurbiprofen completely blocked the effect of evening primrose oil on conduction velocity, resistance to hypoxia, and capillarization. 8 Six main conclusions were reached. First, evening primrose oil rapidly reverses conduction deficits in diabetic rats. Second, the effects of treatment may be very short-lived, suggesting a primary metabolic action. Third, evening primrose oil cannot reverse established changes in hypoxic resistance over 1-month treatment. Fourth, long-term treatment causes angiogenesis, suggesting a vascular action. Fifth, products of cyclo-oxygenase-mediated metabolism are necessary for maintaining vasa nervorum integrity in diabetic rats. Sixth, evening primrose oil probably acts by providing substrate for vasodilator prostanoid synthesis by vasa nervorum.

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Sural nerve oxygen tension in diabetes.

Abstract: Peripheral nerve oxygen tensions were assessed in vivo by using microelectrodes to measure endoneurial oxygen tension in exposed sural nerve. In 11 diabetic patients with chronic sensorimotor neuropathy the mean endoneurial oxygen tension was 39 7

Cited by 246 publications

References 7 publications

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

The potential contribution of endothelin-1 to neurovascular abnormalities in streptozotocin-diabetic rats

The effects of evening primrose oil on nerve function and capillarization in streptozotocin‐diabetic rats: modulation by the cyclo‐oxygenase inhibitor flurbiprofen

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