Nerve Blood Flow and Oxygen Delivery In Normal, Diabetic, and Ischemic Neuropathy

Low, Phillip A.; Lagerlund, Terrence D.; McManis, Philip G.

doi:10.1016/s0074-7742(08)60283-4

Cited by 199 publications

(136 citation statements)

References 151 publications

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“…4 B) recorded during the hydrogen clearance measurements, with significant reductions in diabetic and ARI-treated diabetic groups compared to non-diabetic rats (p < 0.05). Differences in perfusion pressure may have contributed to the flow changes with diabetes and treatment as vasa nervorum has a minimal capacity for pressure autoregulation [27]. When this is taken into account by expressing the data as endoneurial nutritive vascular conductance (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The fitting procedure gave r 2 values within the range 0.997-1.000 for all individual curves in this study. The slow exponent was taken to reflect nutritive capillary flow, and the fast exponent non-nutritive flow [27]. Composite (total) endoneurial flow was defined as the weighted sum of fast and slow components.…”

Section: Methodsmentioning

confidence: 99%

“…This would result in an apparent relative decrease in nerve blood flow for diabetic rats. However, the application of the microsphere method to the measurement of nerve blood flow is questionable [24,27,28,41] and other techniques that do not involve nerve exposure also show reduced nerve blood flow in diabetic rats [42]. Whether or not an operative procedure causes a significant inflammatory response depends critically on the degree of tissue trauma.…”

Section: Methodsmentioning

confidence: 99%

“…NADPH is also necessary for nitric oxide synthesis and the maintenance of vascular tone. These latter mechanisms have been linked to reduced nerve perfusion and oxygen supply [6,10,[23][24][25][26] which make major contributions to nerve dysfunction in diabetic patients and experimental models [27][28][29]. In contrast, other hypotheses consider the second half of the polyol pathway, conversion of sorbitol to fructose by sorbitol dehydrogenase, as the most important in the pathogenesis of diabetic complications including neuropathy.…”

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confidence: 99%

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Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

et al. 1997

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Elevated polyol pathway activity has been implicated in the development of diabetic complications, including neuropathy [1]. In diabetic models, inhibitors of the first enzyme in the pathway, aldose reductase, prevent or correct nerve conduction velocity (NCV) and regeneration deficits [2][3][4][5][6][7][8][9][10][11][12][13]. Clinical trials of aldose reductase inhibitors (ARIs) have shown modest improvements in neurological symptoms, NCV, sensory measures, and an increase in nerve fibre regeneration [14-17] despite a less effective polyol pathway blockade than was found necessary for functional effects in animal studies [6,10,18].Several hypotheses have been advanced to explain the action of ARI. Some putative mechanisms are primarily dependent on the first half of the polyol pathway, conversion of glucose to sorbitol by aldose Diabetologia (1997) 40: 271-281 Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats Summary Aldose reductase inhibitors (ARIs) attenuate diabetic complications in several tissues, including lens, retina, kidney, blood vessels, striated muscle and peripheral nerve. However, it is unclear whether their action in diabetes mellitus depends directly on inhibiting the conversion of glucose to sorbitol by aldose reductase or indirectly by reducing the sorbitol available for subsequent metabolism to fructose by sorbitol dehydrogenase. To identify the polyol pathway step most relevant to complications, particularly neuropathy, we compared the biochemical effects of a sorbitol dehydrogenase inhibitor, WAY-135 706, (250 mg ⋅ kg −1 ⋅ day −1 ) and an ARI, WAY-121 509, (10 mg ⋅ kg −1 ⋅ day −1 ) on a variety of tissues, and their effects on nerve perfusion and conduction velocity. After 6 weeks of untreated streptozotocin diabetes, rats were treated for 2 weeks. Sorbitol was elevated 2.1-32.6-fold by diabetes in lens, retina, kidney, aorta, diaphragm, erythrocytes and sciatic nerve; this was further increased (1.6-8.2-fold) by WAY-135 706 whereas WAY-121 509 caused a marked reduction. Fructose 1.6-8.0-fold elevated by diabetes in tissues other than diaphragm, was reduced by WAY-135 706 and WAY-121 509, except in the kidney. Motor and sensory nerve conduction velocities were decreased by 20.2 and 13.9 %, respectively with diabetes. These deficits were corrected by WAY-121 509, but WAY-135 706 was completely ineffective. A 48.6 % diabetes-induced deficit in sciatic nutritive endoneurial blood flow was corrected by WAY-121 509, but was unaltered by WAY-135 706. Thus, despite profound sorbitol dehydrogenase inhibition, WAY-135 706 had no beneficial effect on nerve function. The data demonstrate that aldose reductase activity, the first step in the polyol pathway, makes a markedly greater contribution to the aetiology of diabetic neurovascular and neurological dysfunction than does the second step involving sorbitol dehydrogenase. [Diabetologia (1997) 40: ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

et al. 1997

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“…Previous studies have shown that decrease in No availability or action in the nerves associated with decrease conduction velocity by increasing vasoconstriction (Kihara and Low, 1995) leading to reduced peripheral nerve perfusion which in turns causes endoneurial hypoxia, which is a major factor in the etiology of diabetic neuropathy in patients and animal models (Low et al, 1989;Tesfaye et al, 1994;Cameron and Cotter, 1994).…”

Section: Ajptmentioning

confidence: 99%

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Bin-Jaliah¹

2014

American Journal of Pharmacology and Toxicology

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It was shown that hyperglycemia in diabetic patients is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the development of diabetic peripheral neuropathy. A substantial number of studies have shown that antioxidant treatment are promising therapeutics that can prevent or correct reduced motor nerve conduction in diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and streptozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum glucose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction studies of the sciatic nerves of these rats showed decrease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin-E or L-arginine) corrected serum glucose to control values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg −1 and 600 mg kg −1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg −1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion that diabetic peripheral neuropathy is a multifactorial complication, caused by hyperglycemia, oxidative stress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in higher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.

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Efficacy of limb cooling on the salvage of peripheral nerve from ischemic fiber degeneration

et al. 1996

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Since peripheral nerve has a large ischemic safety factor, hypothermia, by reducing metabolic demands, it is potentially an efficacious technique to rescue nerve from ischemic fiber degeneration (IFD). We therefore evaluated the influence of temperature on the severity of IFD resulting from a standard ischemic stress. Ischemia to the left sciatic nerve in the rat was produced by embolization of 2 × 106 microspheres (14 μm) into its supplying arteries. The limb was embolized at three temperatures, 37°C, 32°C, and 28°C and was maintained at each temperature for an additional 4 h. End points, evaluated 7 days after embolization, for the embolized limb were: (1) behavioral scores, 0–11 in increasing limb function; (2) compound nerve action potential of sciatic‐tibial nerve; (3) sciatic nerve blood flow (NBF, in mL/100 g/min); and (4) histologic grade, expressed as percentage of fibers undergoing IFD (0 = < 5% 1 = 5–25% 2 = 26–50% 3 = 51–75% 4 = >75%). NBF was reduced in all groups, varying with temperature, and all indices of nerve structure and function were significantly improved with hypothermia. We conclude that hypothermia, easily achievable in a limb nerve, is highly efficacious in the rescue of nerve from IFD. These findings are of clinical relevance. © 1996 John Wiley & Sons, Inc.

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Nerve Blood Flow and Oxygen Delivery In Normal, Diabetic, and Ischemic Neuropathy

Cited by 199 publications

References 151 publications

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Efficacy of limb cooling on the salvage of peripheral nerve from ischemic fiber degeneration

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