scholarly journals Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Lawrence Coppey ◽  
Bao Lu ◽  
Craig Gerard ◽  
Mark A. Yorek
Keyword(s):  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Neutral Endopeptidase ◽  
Neural Function ◽  
Fiber Density ◽  
Thermal Nociception ◽  
Intraepidermal Nerve Fiber Density ◽  
Deficient Mice ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

We have demonstrated that treating diet-induced obese (DIO) mice with the vasopeptidase inhibitor ilepatril improved neural function. Vasopeptidase inhibitors block angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity. We propose that increased activity of ACE and NEP contributes to pathophysiology of DIO. To address this issue C57Bl/6J mice or mice deficient in NEP were fed a high-fat diet and treated with ilepatril, enalapril, ACE inhibitor, or candoxatril, NEP inhibitor, using both prevention and intervention protocols. Endpoints included glucose utilization and neural function determination. In the prevention study glucose tolerance was impaired in DIO C57Bl/6J mice and improved with ilepatril or enalapril. Sensory nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density were impaired in DIO C57Bl/6J mice and improved with ilepatril or candoxatril. In the intervention study only enalapril improved glucose tolerance. Sensory nerve conduction velocity and intraepidermal nerve fiber density were improved by all three treatments, whereas thermal nociception was improved by ilepatril or candoxatril. In NEP-deficient mice DIO impaired glucose utilization and this was improved with enalapril. Nerve function was not impaired by DIO in NEP-deficient mice. These studies suggest that ACE and NEP play a role in pathophysiology associated with DIO.

Treatment with Actovegin® Improves Sensory Nerve Function and Pathology in Streptozotocin-Diabetic Rats via Mechanisms Involving Inhibition of PARP Activation

2011 ◽  
Vol 120 (03) ◽  
pp. 132-138 ◽  
Author(s):  
A. Dieckmann ◽  
M. Kriebel ◽  
E. Andriambeloson ◽  
D. Ziegler ◽  
M. Elmlinger
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Sensory Nerve Conduction Velocity ◽  
Fiber Density ◽  
Parp Activation ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

AbstractDiabetic neuropathy is one of the most severe complications of diabetes, affecting approximately one-third of diabetic patients. We investigated the potential neuroprotective effect of Actovegin®, a deproteinized hemoderivative of calf blood, in an animal model of diabetic neuropathy.A single intravenous injection of streptozotocin (STZ, 55 mg/kg) was used to induce experimental diabetes in male Sprague-Dawley rats. Actovegin® (200 or 600 mg/kg) was administered intraperitoneally from day 11 to day 40 post-STZ exposure. N-acetylcysteine (NAC) was used as a positive control and was added to drinking water (0.2 g/l) from day 2 until day 40. Measurements to assess efficacy included sensory nerve conduction velocity (SNCV), intraepidermal nerve fiber density (IENFD), and poly(ADP-ribose) content.A decrease (35%) in sensory nerve conduction velocity (SNCV) was seen in STZ-induced diabetic rats from day 10 post-STZ administration and persisted at days 25 and 39. At study completion (day 41), a decrease (32%) in intraepidermal nerve fiber density (IENFD) was found in hind-paw skin biopsies from STZ-rats. Reduced SNCV and IENFD were significantly ameliorated by both doses of Actovegin®. More­over, 600 mg/kg Actovegin® markedly decreased poly(ADP-ribose) polymerase (PARP) activity in sciatic nerves from STZ-diabetic rats as assessed by poly(ADP-ribose) content.Actovegin® improved several para­meters of experimental diabetic neuropathy via mechanisms involving suppression of PARP activation, providing a rationale for treatment of this disease in humans.

scholarly journals Treatment of Streptozotocin-Induced Diabetic Rats with Alogliptin: Effect on Vascular and Neural Complications

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Brian Dake ◽  
Mark A. Yorek
Keyword(s):  
Conduction Velocity ◽  
Nerve Conduction ◽  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Fiber Density ◽  
Dpp Iv ◽  
Intraepidermal Nerve Fiber Density ◽  
Calcitonin Gene ◽  
Nerve Fiber Density

We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.

scholarly journals Effect of Dietary Content of Menhaden Oil with or without Salsalate on Neuropathic Endpoints in High-Fat-Fed/Low-Dose Streptozotocin-Treated Sprague Dawley Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Hanna Shevalye ◽  
Alexander Obrosov ◽  
Mark A. Yorek
Keyword(s):  
Vascular Reactivity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Neural Function ◽  
Menhaden Oil ◽  
High Fat ◽  
Fiber Density ◽  
Thermal Nociception ◽  
Intraepidermal Nerve Fiber Density

In this study, we wanted to extend our investigation of the efficacy of fish oil with or without salsalate on vascular and neural complications using a type 2 diabetic rat model. Four weeks after the onset of hyperglycemia, diabetic rats were treated via the diet with 3 different amounts of menhaden oil with or without salsalate for 12 weeks. Afterwards, vascular reactivity of epineurial arterioles and neuropathy-related endpoints were examined. The addition of salsalate to high-fat diets enriched with 10% or 25% kcal of menhaden oil protected vascular reactivity to acetylcholine and calcium gene-related peptide, motor and sensory nerve conduction velocity, thermal nociception, intraepidermal nerve fiber density, and cornea sensitivity to a greater extent than 10% or 25% menhaden oil alone. Vascular and neural function was maximally protected with diet containing 45% kcal as menhaden oil, and adding salsalate did not provide any additional benefit. Salsalate alone in the high-fat diet of diabetic rats provided minimal protection/improvement of vascular and neural dysfunction. These studies imply that dietary salsalate in combination with lower amounts of menhaden oil can provide greater benefit toward diabetes-induced vascular and neural impairment than menhaden oil alone.

scholarly journals Intraepidermal Nerve Fiber Density in Friedreich’s Ataxia

2018 ◽  
Vol 77 (12) ◽  
pp. 1137-1143 ◽  
Author(s):  
Elisabetta Indelicato ◽  
Wolfgang Nachbauer ◽  
Andreas Eigentler ◽  
Dagmar Rudzki ◽  
Julia Wanschitz ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Fiber Density ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

scholarly journals Intraepidermal nerve fiber density and its application in sarcoidosis

Neurology ◽  
2009 ◽  
Vol 73 (14) ◽  
pp. 1142-1148 ◽  
Author(s):  
M. Bakkers ◽  
I.S.J. Merkies ◽  
G. Lauria ◽  
G. Devigili ◽  
P. Penza ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Fiber Density ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

Neurophysiology and Intraepidermal Nerve Fiber Density in Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) (P03.202)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P03.202-P03.202
Author(s):  
W. David ◽  
A. L. Oaklander ◽  
J. Pan ◽  
P. Novak ◽  
R. Brown ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Autonomic Neuropathy ◽  
Fiber Density ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber
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