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Biomedical subjects

H Nukada

Publications and source records attributed to H Nukada.

At least 37 records · Page 2Linked to original sources
PubMed1993

The susceptibility of rat diabetic nerve to ischemia: increased or decreased?

Diabetic nerve reveals a peculiar paradox between its physiological resistance to ischemia, in conducting impulses for longer than control nerve during ischemia, and its morphological liability to more severe pathological changes of nerve fiber when rendered ischemic. These paradoxical phenomena, however, have never been previously evaluated in the same diabetic rat. In the present study, the effect of ischemia on rat diabetic nerve was assessed both physiologically and morphologically at 2 and 16 weeks after the injection of streptozotocin. At 16 weeks the effects of a rapid normalization of blood glucose by insulin on these phenomena were also evaluated. Two weeks after the induction of diabetes, physiological resistance to ischemia was found, but not morphological vulnerability. After 16 weeks of diabetes, both physiological resistance and morphological vulnerability to ischemia were observed. At this time the administration of insulin had no effect on morphological vulnerability, but shortened the time of preservation of nerve action potentials during ischemia although it was not normalized. These findings indicate that the morphological liability of diabetic nerve to ischemia is most likely due to a combined effect of systemic complications of chronic hyperglycemia. By contrast a substantial component of resistance to ischemic conduction failure appears to be related to rapidly reversible metabolic derangement due to hyperglycemia. The study demonstrates coexistence of physiological resistance and morphological vulnerability to ischemia in rat diabetic nerve, and implies that different factors are involved in these paradoxical phenomena.

Action Potentials↗
PubMed1993

Vasodilating effect of dipyridamole on rat endoneurial vessels: morphometric study.

Ischaemia plays an important role in the pathogenetic mechanism of various neuropathies. To study the possible vasodilating effects of dipyridamole on peripheral nerve vessels, morphometric analysis of endoneurial vessels was undertaken in rat sciatic and tibial nerves after chronic dipyridamole treatment. Each rat was injected with 4 mg/kg of dipyridamole intraperitoneally twice daily for 5 days/week and once daily during the weekend for a period of 6 weeks. The mean luminal area and perimeter of endoneurial vessels in the sciatic nerve were significantly greater in dipyridamole-treated animals than in controls. The total fascicular area and densities of endoneurial vessels were not significantly different between experimental and control groups. This study demonstrated that daily administration of dipyridamole over a 6 week period caused endoneurial vessels to dilate resulting in increased luminal area and perimeter. Dipyridamole might be a potent therapeutic agent for peripheral neuropathies attributed to nerve ischaemia.

Animals↗
PubMed1993

Spatial distribution of nerve injury after occlusion of individual major vessels in rat sciatic nerves.

In an attempt to better understand the spatial distribution of ischemic injury secondary to occlusion of major arteries, we measured nerve blood flow (NBF) and studied morphologic changes at various levels distal to the ligature site. Arterial ligation of the femoral, internal iliac, or superior gluteal artery was preceded and followed by measurement of NBF using laser Doppler flowmetry which helped identify "watershed areas" and guided the sampling process as nerves were examined pathologically and areas of injury were identified. Femoral artery ligation produced the most severe ischemia, focally reducing NBF by 80% in the tibial nerve at a level just below the knee. Within these ischemic nerve segments there were degenerative changes of nerve fibers seen mainly in the subperineurial region. Ligation of the internal iliac artery caused an approximately 60% reduction in NBF at the upper and mid-thigh levels of the sciatic nerve which resulted only in endoneurial edema in tissue taken at this level. Following superior gluteal artery ligation. NBF was reduced by only 20% at the pelvic level of the sciatic nerve and there was neither endoneurial edema nor fiber abnormalities. This study demonstrates the watershed pattern of ischemic injury associated with single vessel ligation by correlating neuropathologic change with quantitative measures of local nerve blood flow. The data further support the concept that mild levels of ischemia cause endoneurial edema, while moderate levels of ischemia produce demyelination and severe ischemia produces Wallerian degeneration.

Animals↗
PubMed1993

Dichotomous response of whole blood viscosity in streptozotocin-diabetic rats.

Abnormalities of blood rheology may play an important role in the underlying mechanism of the development of diabetic complications. Although streptozotocin (STZ)-induced diabetic rats have been used extensively in the investigation of diabetic complications, blood rheological alterations in this model have not previously been assessed. To assess one aspect of blood rheology, we repeated whole blood viscosity (WBV) measurements at 4, 8, 12 and 16 weeks after the STZ injection in rats. Nine of fifteen diabetic rats showed increased WBV after the induction of diabetes. Although these rats had a higher haematocrit, the increase in WBV was maintained after correction to a standard haematocrit. Percentage changes of WBV were significantly greater in these diabetic rats than in control rats at low shear rates (0.1s-1 and 1.0s-1), but not at high shear rates. In contrast, WBV was lowered at all shear rates after the injection of STZ in the remaining six diabetic rats which had lower haematocrit, severe weight loss and high mortality; no rats survived for 16 weeks post-injection. Animals in this group may be implicated in the high mortality among STZ-diabetic rats. Although there was a clear distinction of rheological and clinical pictures between these two groups of STZ-diabetic rats, blood glucose and HbA1 concentrations did not differ significantly. This study demonstrates a dichotomy in blood viscosity response to STZ-induced diabetes.

Animals↗
PubMed1992

Mild ischemia causes severe pathological changes in experimental diabetic nerve.

Nerve ischemia is considered one of etiological factors in the development of structural changes in peripheral nerves associated with diabetes mellitus. To assess the effect of mild ischemia on diabetic nerve, a subthreshold dose of polystyrene microspheres was injected intraarterially to occlude microvessels of the sciatic nerve and its branches in 20-week streptozotocin-induced diabetic and control rats. Diabetic sciatic and tibial nerves showed severe pathological change of myelinated fibers, whereas nondiabetic nerves were normal or had minor structural abnormalities. Morphometrical evaluation confirmed a greater frequency of abnormal myelinated fibers in diabetic nerves especially in central fascicular regions. The results indicate that diabetic nerve has an increased morphological susceptibility to nerve ischemia. Endoneurial hypoxia, which may result from hemorheological and vascular abnormalities, is likely to cause a lowered threshold to ischemic tolerance in diabetic nerve. This increased vulnerability to ischemia may render diabetic nerve unduly susceptible to hyperglycemia-induced systemic tissue abnormalities.

Animals↗
PubMed1992

Perineurial window: demyelination in nonherniated endoneurium with reduced nerve blood flow.

The perineurial window, created by surgical incision of the perineurial sheath allowing its contents to herniate into the epineurial space, provides an experimental model of primary demyelination, the cause of which is unclear. Because the injury is localized and involves distortion of tissue at the lesion site, ischemia is suspected as a cause of demyelination. To study the mechanism of demyelination in the perineurial window model, we measured nerve blood flow (NBF) with a laser Doppler flowmeter before and after perineurial rupture in rat sciatic nerve and assessed the spatial distribution of demyelinated fibers, particularly in the nonherniated portion of the endoneurium. Nerve blood flow at the site of the perineurial window was reduced significantly with an average level of NBF approximately 50% of presurgical values 10 minutes, 60 minutes and 6 hours after surgery. By light microscopic examination, most nerve fibers that herniated through the perineurial window underwent demyelination by 7 days. In addition, focal lesions of subperineurial demyelination were found in the nonherniated endoneurium in the adjacent subperineurial region and proximally and distally to the perineurial window. Endoneurial vessels adjacent to the perineurial incision appeared to be compressed. We suggest that ischemia contributes to the process of demyelination in the perineurial window model.

Animals↗
PubMed1990

Hereditary cerebellar degeneration with downbeat nystagmus. A case and it's treatment.

We present a female patient of 48 years with downbeat nystagmus (DBN), moderate impairment of coordination testing and a family history of cerebellar ataxia. We report that a single 2 mg dose of clonazepam (following Currie & Matsuo) resulted in a virtual disappearance of nystagmus and of the patient's symptom of oscillopsia. This result is interpreted in terms of current models of DBN.

Cerebellar Ataxia↗
PubMed1990

[Ischemic neuropathy].

Ischemia plays an important role in the development of neuropathies associated with various disorders, such as peripheral vascular occlusive diseases, necrotizing vasculitides, diabetes mellitus and nerve compression or trauma. Although a multiple mononeuropathy or an asymmetrical polyneuropathy is the usual clinical presentation of ischemic neuropathy, some patients present with a neuropathy that is mainly distal and symmetrical. Pathologically, nerve ischemia results in focal or multifocal central fascicular or sector fiber degeneration. These ischemic lesions tend to begin at mid-upper arm or midthigh level, which is the watershed zone of poor perfusion, and become more diffuse distally. Nerve ischemia at the level of distal small fascicles often induces sub-perineurial crescent lesion rather than central fascicular fiber degeneration. Physiologically, reduced nerve blood flow with endoneurial hypoxia has been demonstrated in experimental diabetic and galactose neuropathies. Endoneurial ischemia/hypoxia in galactose neuropathy appears to be due to increased intercapillary distances and constriction of trans-perineurial vessels resulting from endoneurial edema. Although acute ischemic neuropathy has been well investigated, little is known about functional or structural responses of peripheral nerve to chronic ischemia.

Diabetic Neuropathies↗
PubMed1989

Chronic paroxysmal hemicrania.

Chronic paroxysmal hemicrania consists of unilateral paroxysmal headaches, commonly in women, and relieved by indomethacin. Two patients with the condition are reported, one of whom had essential thrombocythaemia and the headaches remitted when the platelet count returned to normal. Platelet function may be worth exploring in these headaches.

Adult↗
PubMed1989

Is ischemia implicated in chronic multifocal demyelinating neuropathy?

We describe a patient with chronic multifocal demyelinating neuropathy associated with persistent conduction block. Multifascicular lesions in sural nerve included a complete loss of myelinated fibers, demyelination, remyelination, onion bulb formation, and axonal attenuation. On the basis of these morphometric results we hypothesize that nerve ischemia may be involved in the pathogenesis of chronic multifocal demyelinating neuropathy.

Brain Ischemia↗
PubMed1988

Post-traumatic endoneurial neovascularization and nerve regeneration: a morphometric study.

Neovascularization would be expected to play an important role in regeneration after nerve injury, but its mechanism is poorly understood. Quantitative investigations of endoneurial capillaries and myelinated fibers 5 and 15 mm distal to different types of nerve injury have therefore been performed. This study demonstrated that numbers of endoneurial capillaries were significantly increased at the 5 mm level 2, 4, 6 and 8 weeks after crush, transection and ischemic lesions, but not following permanent axotomy. Late neovascularization associated with delayed nerve regeneration was found following nerve ischemia. These results suggest that neovascularization following nerve injury is dependent on two variables, the degree of nerve regeneration and the severity of ischemia. Axonal outgrowth appears to be an important determinant of post-traumatic new capillary formation, while nerve ischemia causes both delayed neovascularization and nerve regeneration.

Animals↗
PubMed1988

Neuropathy in multiple symmetric lipomatosis. Madelung's disease.

With increasing age, peripheral neuropathy becomes more common in multiple symmetric lipomatosis (MSL) and the principal cause of severe disability. High alcohol consumption is frequently associated and the peripheral neuropathy of MSL is often attributed to alcoholism. In this study, sural nerve biopsies from MSL patients revealed an absence of acute axonal degeneration, a significant shift to the left of myelinated fibre diameter distributions, reduced indices of axonal and nerve fibre circularity, and an increase in myelin periodicity. This pathology supports the view that the neuropathy of MSL is not alcohol-induced but that a chronic distal axonopathy is an integral part of the MSL syndrome. Biochemical observations suggest a defect in catecholamine-stimulated lipolysis in MSL at a membrane level, possibly in the amount or function of Gs membrane protein or in the catalytic unit of adenylate cyclase. Evidence is presented that the frequent association of MSL with alcoholism is on the basis of an additional ethanol-induced membrane lesion involving beta-adrenergic receptors.

Adult↗
PubMed1987

Acute ischemia causes axonal stasis, swelling, attenuation, and secondary demyelination.

Microsphere embolization of rat sciatic nerve capillaries results in a central fascicular ischemic core. Twenty-four hours after microembolization, the pathological alterations along the length of 55 myelinated fibers were reconstructed by computer imaging of 2,000 serial semi-thin epoxy sections of a tissue block that extended from just above and into an ischemic core. From proximal to distal, the typical sequence of pathological alterations was: normal----swollen dark axons + thin myelin or demyelination----attenuated axons----axon cytolysis (46 fibers) or normal axons (9 fibers). Because organelle accumulation and axonal swelling were the earliest and most proximal pathological lesions, we infer that regional hypoxia causes axonal stasis as a primary event. Demyelination was found in fibers showing swollen dark and attenuated axons. These findings suggest that axons are selectively vulnerable to acute ischemia and that, depending on severity, the fibers either undergo axonal degeneration or transitory structural alterations without axonal degeneration, the latter consisting of axonal changes and secondary demyelination.

Animals↗
PubMed1986

Neovascularization after ischemic nerve injury.

Because angioneogenesis is associated with wound repair, neovascularization may play an important role in regeneration after nerve injury. This hypothesis was tested in the present study in which the number and distribution of endoneurial capillaries were determined 6 weeks after ischemic nerve injury. The density of capillaries was increased in the central fascicular regions of the distal sciatic and proximal tibial nerves at sites of ischemic injury. This was accompanied by a decrease in intercapillary distance. Neovascularization may be a response to ischemia or a consequence of nerve degeneration or regeneration, the mechanisms of which are poorly understood.

Animals↗
PubMed1986

Axonal caliber and neurofilaments are proportionately decreased in galactose neuropathy.

Feeding galactose to rats induces nerve conduction abnormalities, increased levels of nerve galactitol, endoneurial edema, elevated pressure and hypoxia of endoneurial fluid, and pathological abnormalities of nerve fibers. To investigate the cellular mechanisms of the fiber lesions and their possible relationship to alterations in the nerve microenvironment, rat peroneal nerves were morphometrically evaluated eight months after the commencement of galactose feeding. Whereas the density of neurofilaments (NF/micron2) in the transverse axonal area of myelinated fibers was not significantly different between the nerves of galactose-fed and control rats, axonal areas and the number of NF/axon, when related to myelin spiral length, were significantly less in nerves of galactose-fed rats. Myelin alterations, characteristic of axonal atrophy, were also significantly increased. The present data provide evidence of a proportionate decrease in axonal caliber and the number of NF/axon in myelinated fibers in experimental galactose neuropathy, suggesting that galactose induces fibers in experimental galactose neuropathy, suggesting that galactose induces either decreased NF synthesis, assembly or transport. The possible role of microenvironmental alterations, including endoneurial hypoxia and hyperosmolarity, in the production of this axonal atrophy is discussed.

Animals↗
PubMed1986

Increased susceptibility to ischemic damage in streptozocin-diabetic nerve.

Nerve ischemia, both acute and chronic, may contribute to diabetic neuropathies, but the pathogenesis remains obscure. The vulnerability of diabetic nerve to ischemia was assessed by ligating arteries of supply of rat sciatic nerve after 20 wk of streptozocin-induced diabetes. In the first 24 h after the arterial ligations, severe and more rapidly occurring clinicopathological abnormalities were invariably seen in diabetic nerves, but these findings were less severe in nondiabetic nerves. The results imply that peripheral nerve in diabetes mellitus is more subject to ischemia than normal nerve. This phenomenon may ensue from endoneurial hypoxia and play an important role in the development of diabetic neuropathies.

Animals↗
PubMed1985

Endoneurial oxygen tension and radial topography in nerve edema.

Endoneurial edema occurs in numerous human and experimental neuropathies. We tested the hypothesis that the resultant increase in intercapillary distance (ICD) may result in endoneurial hypoxia. Experimental galactose neuropathy (EGN) was chosen since in this model, edema is due to the accumulation of galactitol, which does not directly damage nerve fibers, so that it was possible to study the role of endoneurial edema alone. We measured endoneurial oxygen tensions (PnO2) using oxygen-sensitive microelectrodes and related PnO2 radial topography to ICD. We also determined local oxygen consumption (VLO2) and critical PnO2(PcritO2). EGN and age-matched controls were studied at 4 months. (1) Caudal nerve conduction velocity was reduced in EGN. (2) The PnO2 values were reduced in EGN and the PnO2 histogram was shifted into the hypoxic range. These changes were paralleled by a significant increase in ICD in EGN. (3) The radial topography of PnO2 in EGN differed from the relatively uniform distribution in control nerves. In EGN the subperineurial PnO2 was significantly lower than the PnO2 at the center of the fascicle. These changes were paralleled by a significantly greater increase in ICD in the periphery. (4) That the PnO2 reduction in EGN was significant is suggested by the marked reduction in VLO2 and the large percentage (greater than 75%) of intrafascicular regions that fell below PcritO2 in EGN.

Animals↗