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H C Powell

Publications and source records attributed to H C Powell.

At least 91 records · Page 5Linked to original sources
PubMed1986

Reduced nerve blood flow in edematous neuropathies: a biomechanical mechanism.

Reduced nerve blood flow has been reported in two experimental neuropathies in which edema is an early and significant finding. While the mechanisms of fluid accumulation differed, both resulted in increases of endoneurial fluid pressure up to five times the normal value. As increased endoneurial fluid distends the nerve, the perineurial sheath resists expansion and endoneurial fluid pressure increases. The semirigid perineurium is also a conduit for regional nutritive vessels which provide the greater part of peripheral nerve blood flow. Engineering structural analysis of blood vessels entering the endoneurium suggests that moderate elevations in endoneurial fluid pressure can deform cylindrical vessels in the perineurium into elliptical shapes by creating circumferential elongation and longitudinal compression of the vessels which reduce the cross-sectional area of the lumen. We propose that the pathogenesis of reduced nerve blood flow in edematous neuropathies is linked to the unique structure of the peripheral nerve perineurium and the nerve vasculature, in particular to deformation of anastomotic vessels traversing it.

Animals↗
PubMed1986

Abnormal nerve regeneration in galactose neuropathy.

Nerve regeneration across a 10 mm gap through an implanted silicone tube was delayed in galactose-fed rats two and four weeks after transecting the nerve. This experimental metabolic neuropathy resembles diabetic neuropathy in which nerve regeneration is also delayed. Experiments were performed by introducing opposite ends of divided sciatic nerves into close-fitting silicone tubes, leaving a 10 mm gap. Growth of neurites across this gap was monitored by electron microscopy performed in sections at regular intervals of 2 mm from proximal to distal stumps. After two weeks some difference was apparent; axons advanced 1.4 +/- 0.4 mm in galactose-fed rats versus 3.5 +/- 1.5 mm in controls. Myelination did not progress beyond 1 mm in galactose-fed rats. Differences were greater between the two groups at four weeks. The growth of axons in galactose rats was 3.5 +/- 0.2 mm versus 9.4 +/- 0.1 mm in control nerves. In addition the size of the regenerating stump was much greater in control rats. Qualitative differences were also noticed during electron microscopic comparison of control and galactose-treated rats. The dystrophic axons seen in treated rats had abnormal electron-dense organelles, lamellated bodies, vesicles and tubular structures, as well as numerous glycogen granules. Abnormalities of spatial orientation were also noted. Unlike control axons which grew parallel with the long axis of the tube, regenerating axons in experimental animals were seen deviating from the axis at 90 degrees angles. Both immature sprouts and myelinating axons showed abnormal plasticity. Ultrastructural differences were also noted in Schwann cells, macrophages and vessels.

Animals↗
PubMed1986

The role of 2-chloroprocaine and sodium bisulfite in rat sciatic nerve edema.

In order to evaluate the possible mechanisms of local anesthetic toxicity, the rat sciatic nerve was exposed to various solutions including Nesacaine (containing the antioxidant sodium bisulfite), 2-chloroprocaine in the Nesacaine vehicle (0.2% sodium chloride), 0.2% sodium bisulfite in 0.2% sodium chloride, or 0.2% sodium chloride alone. All solutions were pH balanced between 2.9 and 3.2. Forty-eight hours (h) following extraneural administration of 1 ml volumes, significant edema was produced by all solutions containing 3% 2-chloroprocaine, but not with 0.2% bisulfite in sodium chloride or with sodium chloride alone. Intrafascicular administration of five to ten microliter volumes of these solutions produced edema at 48 h in all cases, but the highest levels were observed with Nesacaine and the lowest levels with 0.2% bisulfite. The results of this study implicate the local anesthetic 2-chloroprocaine in the production of nerve edema, which is inconsistent with other reports that the toxicity of Nesacaine-CE can be attributed to the antioxidant bisulfite.

Anesthetics, Local↗
PubMed1986

Pathology of experimental nerve compression.

Acute, graded, nerve compression was applied to the sciatic nerves of 91 rats in whom an inflatable miniature Plexiglass compression device had been implanted in the thigh. The experiment was designed to study the pathogenesis of lesions in the nerve entrapment syndrome. Under general anesthesia, external pressures of 80 mm of Hg, 30 mm of Hg and 10 mm of Hg were used to compress nerves for 2 hours. Identical compression devices were placed around the contralateral sciatic nerves but remained uninflated so that these nerves could be used as controls. Nerves were excised at intervals of 4 and 24 hours, and at 1, 2, 5, 6, 7, 10, 14, and 28 days, and full thickness transverse sections were made from Araldite blocks. The first pathologic change was nerve edema which was observed at all time points and correlated with the severity of axonal injury. Axonal lesions were predominant in nerves exposed to 80 mm of Hg (7.5 +/- 1.9 nerve fibers per high power microscopic field (HPF)) while nerves compressed at 30 mm of Hg showed fewer damaged axons (2.6 +/- 1.4 per HPF). Demyelination was the predominant lesion in nerves subjected to 30 mm of Hg and was commonly present in nerves around which the compression chamber remained uninflated. Electron microscopy revealed demyelination to be associated with Schwann cell necrosis. The topography of nerve fiber injury was remarkable; subperineurial fibers were often damaged after compression of nerves in which nerve fibers at the core of the fascicle remained unaffected. The findings suggest that local external compression causes ischemia in nerve fibers served by transperineurial vessels, with severe compression causing axonal damage, while lesser degrees of compressive injury are associated with demyelination.

Animals↗
PubMed1986

Neurotoxicity of local anesthetics: altered perineurial permeability, edema, and nerve fiber injury.

A quantitative, in situ experimental method was developed employing the rat sciatic nerve to study the neurotoxicity of local anesthetic solutions applied directly to an intact peripheral nerve bundle. One-milliliter volumes of 2-chloroprocaine, 3%; tetracaine, 1%; lidocaine, 2%; bupivacaine, 0.75%; or sodium chloride, 0.2%; were injected with a 30-gauge needle beneath the mesoneurium but exterior to the epineurium. The wound was closed and the animals were normally maintained until the nerves were reexposed for quantitative biophysical and morphologic testing 24 h to 4 weeks later. The results indicate that topically applied 2-chloroprocaine and tetracaine produce significant endoneurial edema 48 h after treatment. Horseradish peroxidase was used to verify increased permeability of the perineurium. Endoneurial fluid pressure was significantly increased in edematous nerves. Electron microscopy revealed abnormal mast cells and proliferation of endoneurial fibroblasts in addition to Schwann cell injury and axonal dystrophy. This study shows that extrafascicular administration of clinically used concentrations of local anesthetic solutions can alter perineurial permeability, producing changes in the endoneurial environment that are associated with neurotoxic injury. Perineurial and endoneurial fibrotic changes may be a late consequence of peripheral nerve injury with anesthetic solutions producing altered perineurial permeability with endoneurial edema.

Anesthetics, Local↗
PubMed1985

Autonomic nerves in experimental allergic neuritis in the rat.

After experimental allergic neuritis (EAN) was induced in 16 male Lewis rats with bovine peripheral myelin and adjuvants, peripheral nerves were examined morphologically at intervals of 12-21 days post inoculation (dpi). Signs of motor involvement were present in ten rats and were first elicited 12 dpi. They ranged from tail droop to complete lower limb paralysis. Autonomic nervous system (ANS) involvement was studied by contrasting morphological findings in the cervical sympathetic nerves (CSN), which are poorly myelinated and vagal nerves (VN) which contain numerous myelinated fibers in the endoneurium. Edema, perivenular infiltrates, and demyelination appeared in the VN of seven of nine neurologically affected rats, while the CSN showed edema and infiltrates in only one rat. ELISA assays were negative for anti-galactocerebroside antibody, and electron microscopy failed to show abnormalities of Schwann cells.

Animals↗
PubMed1985

Microangiopathy in human diabetic neuropathy.

Morphological change of endoneurial and perineurial vessels accompanied severe loss of myelinated axons in peripheral nerves of each of 17 patients with diabetic neuropathy. Vascular mural thickening averaged 18.9 +/- 9.9 micron2 in diabetic capillaries (n = 11) vs. 6.9 +/- 4.1 micron2 in controls (n = 7). Electron microscopy revealed vigorous endothelial proliferation as well as thickening and reduplication of basal lamina in each instance. Particular attention was paid to vessels which penetrate the perineurium en route to the endoneurial interstitium, since they provide a major portion of the endoneurial blood supply. Luminal narrowing and mural thickening of these vessels was compounded by basal laminar thickening of the perineurium. Fenestrated endoneurial capillary endothelium was noted in one case. Both demyelination and axonal degeneration were observed with intra-axonal glycogen accumulation in some axons. Morphometric analysis revealed extensive myelinated nerve fiber loss in diabetic nerves. These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.

Blood Vessels↗
PubMed1985

Laser injury of peripheral nerve: a model for focal endoneurial damage.

A model of endoneurial oedema is presented which produces localised nerve fibre injury including Wallerian degeneration, endoneurial oedema and increased endoneurial fluid pressure. A carbon dioxide laser was used to irradiate rat sciatic nerve and quantitative results were collected 2 days and 6 days after irradiation. The increase in endoneurial fluid pressure is compared with other models of Wallerian degeneration in which the entire fascicle was involved to aid in a comparative study of the role of oedema in neuropathy.

Animals↗
PubMed1984

Competence of nerve tissue as distal insert promoting nerve regeneration in a silicone chamber.

A new peripheral nerve forms across a 10 mm gap within a silicone chamber regeneration model when the distal segment of a transected sciatic nerve, connected to its end organs, is sutured into the distal end of the chamber. We have tested the ability of other tissue inserts to support axonal regeneration in the chamber. When an isolated 2 mm piece of sciatic nerve was sutured into the distal end, fibrin matrix formation, cell immigration and axonal regeneration were identical to those occurring in the control. When the distal nerve insert was replaced with a 2 mm piece of skin or a ligation, a matrix did not form and subsequent cell immigration and axonal regeneration did not occur. When a 2 mm piece of tendon was inserted, a matrix did form at 1 week, but a structure across the gap was observed at later time periods in only 2 out of 7 chambers. The matrix either dissolved before cells could enter the chamber or did not promote cellular immigration and subsequent axonal regeneration. When the distal end was left open, a matrix formed and cells from the reactive tissue outside the chamber entered the matrix and formed a granulation tissue bridge across the gap. This tissue failed to support axonal regeneration; at 3 weeks, axons stopped 1 mm beyond the proximal stump at the interface with the granulation tissue. Thus, matrix formation and a cellular bridge are necessary but not sufficient to ensure regeneration. Successful regeneration across the silicone chamber gap requires humoral and/or cellular contributions available from peripheral nervous tissue and not from the other tested tissues.

Animals↗
PubMed1984

Microangiopathy of vasa nervorum in dysglobulinemic neuropathy.

Thickening of vessel walls resulting from endothelial proliferation was observed in the vasa nervorum of eleven patients with peripheral neuropathy associated with dysglobulinemia. Electron microscopy showed endothelial proliferation accompanied by abnormal accumulation of masses of intracytoplasmic filaments in each case. Of the eleven patients with dysglobulinemia, nine had monoclonal gammopathy and two were found to have polyclonal elevation of gamma globulin levels. Symptoms of neuropathy characteristically preceded detection of serum protein abnormalities by months to years. Nerve fiber lesions involved primarily the axon in four cases; segmental demyelination was the principal abnormality in the other seven. Both abnormalities were present to some degree in all eleven patients. Biphasic myelinopathy with uniform separation of myelin lamellae attributable to globulin deposition was observed in four cases. The microvascular changes included endothelial cytoplasmic enlargement, virtually obliterating the vessel lumen in many instances, with thickening of pericytes, in which intracytoplasmic filaments were prominent and pinocytotic vesicles numerous. No extracellular filaments were noted, and amyloid stains were negative. Possible effects of these microvascular changes include ischemia resulting from severe vascular luminal narrowing, and altered vascular permeability. Severe loss of axons in this group of neuropathies may be the result of ischemia, whereas altered vascular permeability may admit globulin into the endoneurium, where it may directly affect the myelin sheath and precipitate demyelination.

Adult↗
PubMed1984

Galactose neuropathy: impact of chronic endoneurial edema on nerve blood flow.

Peripheral neuropathy induced by galactose feeding results in endoneurial edema with increased tissue pressure and ultimate demyelination of nerve fibers. To assess the role of ischemia in the pathogenesis of this neuropathy, nerve blood flow was measured 6 months after the start of galactose ingestion, between the onset of edema and nerve fiber changes. Measurement was carried out by a noninvasive technique involving the use of [14C]iodoantipyrine as a radioactive tracer of tissue perfusion. A significant decline in nerve blood flow was found, which correlated positively with increased nerve water content as quantified by a microgravimetric technique. We sought to establish the pathogenic role of nerve edema in the development of schwannopathy and demyelination by morphological examination. It was found that Schwann cells appeared normal in areas of the peripheral nervous system in which edema does not occur, such as spinal ganglia and roots, whereas in regions in which there was edema, massive glycogen accumulation in Schwann cells and demyelination occurred. These findings suggest that edema, rather than hyperactivity in the sorbitol pathway, is responsible for the pathological changes in galactosemic neuropathy and that ischemia resulting from edema and increased endoneurial fluid pressure is the mechanism responsible for fiber injury.

Animals↗
PubMed1984

Axonopathy and microangiopathy in chronic alloxan diabetes.

A significant reduction in the myelinated nerve fiber population was observed during quantitative electron-microscopic examination of peripheral nerves in chronic alloxan diabetic rats. Dystrophic axonal abnormalities and regenerating fibers were more numerous in diabetics than age-matched controls. Schwann cells showed reactive changes including prominent pi granules of Reich and intracytoplasmic filament accumulation. Enumeration of these alterations, however, revealed no significant difference from controls. Endoneurial macrophages in diabetic rats were also filled with lamellar intracytoplasmic inclusions characteristic of a chronic neuropathy. Quantitation of pathologic lesions in teased nerve fibers confirmed the preponderance of axonal over demyelinative disease and showed demyelination to be segmental. Microangiopathy was noted throughout the vasa nervorum of diabetic rats, and quantitative electron microscopy showed endothelial proliferation with doubling of the number of endothelial cells and proportional capillary mural thickening. Swollen, reactive endothelial cells appeared to efface the vascular lumen and may impair capillary perfusion. These microcirculatory changes, in the presence of biochemical and rheologic disturbances may contribute to tissue hypoxia and underly the loss of axons in experimental diabetic neuropathy.

Animals↗
PubMed1984

Antigen-specific demyelination and significance of the bystander effect in peripheral nerves.

In an experiment designed to evaluate bystander demyelination in peripheral nerve, immune reactions to tuberculin and albumin failed to induce demyelination, except in animals previously sensitized to a myelin component. The peripheral nerves of tuberculin-sensitized rats and guinea pigs and rabbits were examined at intervals from 8 to 144 hours after intraneural challenge with purified protein derivative (PPD). The results were compared with the immune reaction produced by endoneurial injection of bovine serum albumin (BSA) in rats sensitized to BSA in Freund's complete antigen (FCA). Tuberculin-sensitized rats responded to endoneurial PPD injection by developing perivascular lymphocytic infiltrates which were most severe 5 days after injection. Albumin-sensitized rats responded within hours of BSA injection, showing severe endoneurial edema due to vasculitis with extravasation of polymorphonuclear leukocytes, red cells, and fibrin. The reaction tapered off within 2 days. No significant demyelination occurred in either group. However, demyelination was elicited when the hapten galactocerebroside (GC) was included in the sensitizing inoculum. Schwann-cell necrosis was visible 2 days after endoneurial challenge injection, and demyelination became extensive 5 days after injection. The findings were compared with those after direct injection of anti-GC-antibody, which produced demyelination by lysis of Schwann cells. In rabbits the occurrence of demyelination correlated with the presence of circulating antibodies to GC.

Animals↗
PubMed1984

Experimental allergic neuritis: demyelination induced by P2 alone and non-specific enhancement by cerebroside.

Experimental allergic neuritis was induced in male inbred Lewis rats immunized with myelin, P2 alone, P2 mixed with galactocerebroside and P2 mixed with glucocerebroside. Neurological deficit started significantly earlier in myelin-immunized rats than in P2-immunized rats. Although myelin-immunized rats appeared most severely affected, differences between the groups in maximum neurological deficit were not significant. The course of the disease of the P2-galactocerebroside-immunized animals did not differ from that of the P2-glucocerebroside-immunized group. Histologically, cellular infiltration and demyelination were more conspicuous 12 days after immunization in the group immunized with myelin than in the other rats. After 21 days, primary demyelination was prominent in all groups: its frequency and severity were similar in the myelin-immunized and P2-immunized animals. The P2-galactocerebroside-immunized group had significantly more frequent demyelination than the P2-immunized group. Wallerian degeneration was prominent in all groups at this stage. We conclude that P2 alone does induce demyelination and that galactocerebroside added to the immunizing emulsion enhances the response but no more than the non-myelin lipid glucocerebroside.

Adjuvants, Immunologic↗
PubMed1983

Spatial-temporal progress of peripheral nerve regeneration within a silicone chamber: parameters for a bioassay.

The spatial-temporal progress of peripheral nerve regeneration across a 10-mm gap within a silicone chamber was examined with the light and electron microscope at 2-mm intervals. A coaxial, fibrin matrix was observed at 1 week with a proximal-distal narrowing that extended beyond the midpoint of the chamber. At 2 weeks, Schwann cells, fibroblasts, and endothelial cells had migrated into the matrix from both nerve stumps. There was a delay of 7-14 days after nerve transection and chamber implantation before regenerating axons appeared in the chamber. At 2 weeks, nonmyelinated axons were seen only in the proximal 1-5 mm of the chamber in association with Schwann cells. Axons reached the distal stump by 3 weeks and a proximal-distal gradient of myelination was observed. These observations define the parameters of a morphologic assay for regeneration in this chamber model which can be used to investigate cellular and molecular mechanisms underlying the success of peripheral nerve regeneration.

Animals↗
PubMed1983

Mapping of the major histocompatibility complex and viral antigens on the plasma membrane of a measles virus-infected cell.

The two measles virus glycoproteins, the hemagglutinin and fusion protein, are expressed on the surfaces of infected cells. Although the two molecules are chemically distinct, they associate on the cell surface, judging from their ability to comigrate (co-cap). However, neither is directly complexed with the major histocompatibility (MHC) gene products, HLA-A, -B, -C or -D, on the plasma membrane, based on results from three distinct assays. First, in tests of capping, these viral glycoproteins failed to comigrate with any HLA determinant. Second, electron microscopy showed that the viral glycoproteins occupied domains on the plasma membrane distinct from MHC gene products; 125I labeling of cell surface determinants and subsequent analysis by immune precipitation and PAGE confirmed this result. Third, incubation of measles virus-infected cells in the presence of monoclonal or polyclonal antibodies to measles virus glycoproteins removed the viral glycoproteins from the cells' surfaces but did not cause a corresponding decrease in amounts of HLA molecules. These results indicate that the hemagglutinin and fusion polypeptides of measles virus lie in close association on the plasma membrane; however, neither is linked with MHC gene products.

Antigens, Viral↗
PubMed1983

Endoneurial fluid is hypertonic. Results of microanalysis and its significance in neuropathy.

A new technique has been developed for the microanalysis of interstitial fluid from peripheral nerve. Energy dispersive spectrometry (EDS) was employed to measure X-ray fluorescence secondary to electron excitation of endoneurial fluid in order to determine the concentration of sodium, chloride, and potassium from 100 picoliter samples collected in situ. Normal Long-Evans (L-E) rats had endoneurial fluid electrolyte values which were higher than serum values and which explained the positive fluid pressure in peripheral nerve interstitium. Ten weeks after starting a diet containing 6% lead carbonate in powdered laboratory chow, endoneurial fluid electrolytes in LE rats were significantly reduced and approached serum electrolyte concentrations. This change occurred subsequent to angiopathy and increased permeability of the blood-nerve barrier. This sensitive new technique should provide previously unattainable data to assess the pathological role and the dynamics of the nerve fiber environment in relationship to early changes in nerve function.

Animals↗