Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats.

Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy.

Pathological Findings of Hourglass-Like Constriction in Spontaneous Posterior Interosseous Nerve Palsy.

We report the pathological findings of hourglass-like fascicular constriction (HLFC) under optical and electron microscopy. A 24-year-old man with spontaneous posterior interosseous nerve palsy was treated by interfascicular neurolysis at 29 weeks after onset. One fascicle in the radial nerve presented severe HLFC with torsion at 5 cm proximal to the elbow.

Hypertension Contributes to Neuropathy in Patients With Type 1 Diabetes.

Background: Diabetic peripheral neuropathy (DPN) can lead to foot ulceration and amputation. There are currently no disease-modifying therapies for DPN. The aim of this study was to determine if hypertension contributes to DPN in patients with type 1 diabetes mellitus (T1DM).

Utility of nerve conduction studies for diagnosis of injury to the medial branch of the superficial radial nerve.

Introduction: The clinical utility of nerve conduction study (NCS) for the distal medial branch of the superficial radial nerve (SRN) has not yet been clarified. Therefore, we investigated the clinical utility of NCS in patients with suspected SRN injury and compared the results with those in healthy control subjects.

Methods: Bilateral NCS of the medial branch of the SRN was performed in two patients with suspected injury of the medial branch of the SRN, and in 20 healthy control subjects.

Transplantation of dental pulp stem cells improves long-term diabetic polyneuropathy together with improvement of nerve morphometrical evaluation.

Background: Although previous reports have revealed the therapeutic potential of stem cell transplantation in diabetic polyneuropathy, the effects of cell transplantation on long-term diabetic polyneuropathy have not been investigated. In this study, we investigated whether the transplantation of dental pulp stem cells (DPSCs) ameliorated long-term diabetic polyneuropathy in streptozotocin (STZ)-induced diabetic rats.

Methods: Forty-eight weeks after STZ injection, we transplanted DPSCs into the unilateral hindlimb skeletal muscles.

Neuropathy in the spontaneously hypertensive rat: An electrophysiological and histological study.

Introduction: Hypertension is identified as a risk factor for development of polyneuropathy. In this study we examined nerve conduction and morphological alteration of peripheral nerves in spontaneously hypertensive rats (SHR).

Methods: Motor nerve conduction velocity (MNCV) in the sciatic-tibial nerve and sensory nerve conduction velocity (SNCV) in the sural nerve were measured.

Ischemia and diabetic neuropathy.

In addition to hyperglycemia and ensuing metabolic changes, vascular abnormalities and ischemia driven by hyperglycemia and metabolic change plays a paramount role for the development of diabetic polyneuropathy. Endothelial dysfunction plays a key role in the initiation of cellular events evolving into the development of vascular complications of diabetes, and is the common denominator between the metabolic and vascular abnormalities detected in diabetes. Diminished production and function of endothelium-derived vasodilators, and the exaggerated production of vasoconstrictors, lead to endothelial dysfunction, resulting in elevated vascular tone, culminating in macro- and microvascular damage.

Therapeutic effect of exendin-4, a long-acting analogue of glucagon-like peptide-1 receptor agonist, on nerve regeneration after the crush nerve injury.

Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system.

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

Ischemic vulnerability in diabetic nerve plays a paramount role in the development of diabetic neuropathy, yet little is known of the underlying mechanism. Diabetes enhances the inflammatory response to ischemia and reperfusion. We investigated pathological characteristics of nerve fibers and endoneurial macrophages along the length of sciatic-tibial nerves before and after ischemia (60 to 90 min) and reperfusion (6h to 7 days) in 8 weeks of STZ-induced diabetic rats.

The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice.

The polyol pathway, a collateral glycolytic process, previously considered to be active in high glucose milieu, has recently been proposed to play a crucial role in ischaemia/reperfusion tissue injury. In this study, we explored the role of the polyol pathway in acute kidney injury (AKI), a life-threatening condition, caused by hindlimb ischaemia, and determined if inhibition of the polyol pathway by aldose reductase (AR) inhibitor is beneficial for this serious disorder. Mice 8 weeks of age rendered hindlimb ischaemic for 3 h by the clipping of major supporting arteries revealed marked muscle necrosis with accumulation of sorbitol and fructose in ischaemic muscles.

Clinical screening of autonomic dysfunction in multiple sclerosis.

Background And Purpose: Multiple sclerosis (MS) can affect the autonomic nervous system. Although exercise may be beneficial for people with MS, those with autonomic dysfunction may have altered heart rate responses to exercise. We investigated the hypothesis that the pattern of increase in heart rate on commencement of a simple cycle test would be different in those participants with MS who had been shown to have autonomic dysfunction on laboratory testing compared with both control participants and MS participants not exhibiting autonomic involvement.

Prolonged ischemic conduction failure after reperfusion in diabetic nerve.

Diabetic nerve exhibits morphological vulnerability to ischemia and reperfusion, in contrast to its physiological resistance to ischemic conduction failure (RICF). To examine the sequence of ischemic conduction failure after reperfusion in diabetic nerve, we measured sciatic-tibial nerve conduction before and during 30-180 min of ischemia and after reperfusion for up to 1 week in streptozocin (STZ)-induced diabetic rats. RICF in diabetic rats was confirmed during ischemia.

Neuroprotective effects of nitrone radical scavenger S-PBN on reperfusion nerve injury in rats.

The nitrone-based free radical scavengers have potent neuroprotective activities in models of stroke in which oxidative stress plays a key role in its development. We examined the effects of S-PBN (sodium 4-[(tert-butylimino) methyl]benzene-3-sulfonate N-oxide), a spin trap nitrone, on reperfusion injury in rat peripheral nerves. Immediately after the onset of 4-h ischaemia in rat right hindlimb, S-PBN was administered via mini-osmotic pumps, containing 2 ml of S-PBN (1.

Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems.

Pyrroloquinoline quinone (PQQ) is a novel redox cofactor recently found in human milk. It has been reported to function as an essential nutrient, antioxidant and redox modulator in cell culture experiments and in animal models of human diseases. As mitochondria are particularly susceptible to oxidative damage we studied the antioxidant properties of PQQ in isolated rat liver mitochondria.

Hypoglycaemic neuropathy: microvascular changes due to recurrent hypoglycaemic episodes in rat sciatic nerve.

Intensive diabetes treatment causes a considerable increase in the number of severe hypoglycaemic episodes which could aggravate the progression of diabetic neuropathy. However, the effect of repeated hypoglycaemic episodes on nerve morphology has never been previously investigated. The aims of the present study were: (i) to establish a rat model of recurrent episodes of severe hypoglycaemia, and (ii) to assess morphological changes after repeated hypoglycaemic episodes in rat sciatic nerves.

Aggravated reperfusion injury in STZ-diabetic nerve.

The streptozocin (STZ)-diabetic nerve manifests increased morphological susceptibility to a superimposed acute ischemic injury, and reperfusion injury exaggerates ischemic nerve pathology. To determine whether STZ-diabetic nerves are susceptible to reperfusion, we evaluated the pathological consequences after 2.5 hours of ischemia followed by 3 and 24 hours of reperfusion in a 20-week STZ-diabetic rat sciatic nerve.

Skin wrinkling for the assessment of sympathetic function in the limbs.

Background: Wrinkling of the skin of the palm and sole is considered to be dependent on the presence of intact sympathetic nervous activity. Loss of sympathetic integrity could be simply and usefully assessed by the absence of wrinkling. To test this hypothesis, the skin wrinkle test was compared with the starch-iodine sweat test and sympathetic skin response (SSR) in patients with abnormal sympathetic function.

Acute inflammatory demyelination in reperfusion nerve injury.

We investigated the pathological appearance of acute inflammation and its role in the development of demyelination in reperfused rat sciatic, tibial, and peroneal nerves after a 5-hour period of near-complete ischemia. Polymorphonuclear neutrophil migration was seen early in the endoneurial lesion. After 18 hours of reperfusion, there was maximal intercellular adhesion molecule-1 expression on endoneurial vessels, and polymorphonuclear neutrophil accumulation was then prominent, reaching a peak 24 hours after reperfusion.

Protein carbonyl formation and tyrosine nitration as markers of oxidative damage during ischaemia-reperfusion injury to rat sciatic nerve.

We have investigated the role of oxidative damage in peripheral nerve ischaemia-reperfusion injury using a rat sciatic nerve model. After 5 h ischaemia blood flow to the sciatic nerve was restarted and markers of oxidative damage measured after various times of reperfusion. As a marker of protein oxidative damage, protein carbonyl formation was measured using a sensitive enzyme-linked immunosorbent assay.

Endoneurial microvascular abnormalities of sural nerve in non-diabetic chronic atherosclerotic occlusive disease.

Neuropathic abnormalities are found in chronically ischaemic limbs associated with non-diabetic atherosclerotic peripheral vascular disease (PVD). In chronic ischaemic neuropathy, microvascular alterations play a key role in its development. We undertook morphometric assessment of endoneurial microvessels in the sural nerves, taken from severely ischaemic amputated legs in nine chronic non-diabetic PVD.

Preservation of skin vasoconstrictor responses in chronic atherosclerotic peripheral vascular disease.

Peripheral neuropathy is often found in ischemic limbs with nondiabetic atherosclerotic peripheral vascular disease (PVD). Sensory symptoms such as burning pain are common in severely ischemic limbs, and sympathectomy has been undertaken for ischemic rest pain. The authors assessed noninvasive quantitative skin vasomotor reflexes in toes and standard systemic cardiovascular autonomic tests in 44 PVD subjects with varying severity of limb ischemia, 30 age-matched control subjects, and nine PVD subjects associated with diabetes.

Carbonyl histochemistry in rat reperfusion nerve injury.

Free radical mediated, site-specific lipid and protein oxidation has been implicated in the pathophysiology of an ischaemic/reperfusion injury. The aim of the present study was to determine whether carbonyl formation could be detected histochemically in reperfused rat sciatic nerves. We also examined the effects of preischaemic alpha-tocopherol supplementation on carbonyl formation in reperfused nerves.

Auditory and inspiratory gasp-evoked sympathetic skin response: age effects.

The sympathetic skin response (SSR) has been employed to assess peripheral neuropathy as an index of sympathetic sudomotor activity. A variety of stimuli can be used to elicit the SSR, but their relative ease of use and reliability have not been studied. In addition, the extent to which age affects the SSR remains unresolved.