Biomedical subjects

H C Powell

Publications and source records attributed to H C Powell.

At least 55 records · Page 3Linked to original sources

PubMed1992

Reduced ciliary neuronotrophic factor-like activity in nerves from diabetic or galactose-fed rats.

This study examined the levels of ciliary neuronotrophic factor (CNTF)-like activity in the sciatic nerve of rats with short-term streptozotocin-induced diabetes or dietary supplementation with 40% galactose. CNTF-like activity, found in nerve extracts by in vitro bioassay, was reduced to 20% of control values after 1 or 2 months of galactose feeding (both P less than 0.01) and to 70% of control values after two months of streptozotocin diabetes (P less than 0.01). These data demonstrate that short-term hyperglycemia or its consequences can reduce extractable levels of Schwann cell-derived neuronotrophic factor and raise the possibility that impaired Schwann cell production of CNTF may contribute to the development of experimental diabetic neuropathy.

Animals↗

PubMed1992

Immunotactoid-like endoneurial deposits in a patient with monoclonal gammopathy of undetermined significance and neuropathy.

An 85-year-old man with a 2-year history of progressive lower limb weakness and paresthesia was found to have an IgG kappa monoclonal gammopathy of undetermined significance (mgus). Clinical and electrophysiological studies revealed a severe distal bilateral symmetrical polyneuropathy. A sural nerve biopsy showed extensive nerve fibre loss with the deposition of large amounts of amorphous material throughout the endoneurium. Electron microscopy showed the deposits to be composed of microtubular structures which were located diffusely throughout the endoneurium. The deposits were also located within the lumina of the vasa nervorum, some of which were undergoing disintegration and rupture with release of the proteinaceous material into the endoneurium. The regions of the nerve in which they appeared most numerous showed more severe nerve fibre damage than other areas. These microtubular structures were also observed in disintegrating vessels and adjacent endoneurium. On immunohistochemistry they stained with antibody to IgG. Identical deposits were found in the dermis in which there was a leucocytoclastic vasculitis. Located in linear arrays within the axons of myelinated and unmyelinated fibres were highly organised tubular structures resembling immunotactoids. Identification of immunotactoid-like structures within the nerve is unique and may be another mechanism by which monoclonal proteins can induce nerve fibre injury.

Aged↗

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↗

PubMed1992

Changes in aldose reductase after crush injury of normal rat sciatic nerve.

The response of aldose reductase (AR) to crush injury was studied in normal rat sciatic nerve. Enzyme activity and immunoreactivity of AR were determined at intervals of 1, 5, 14, 28, and 35 days after crush and correlated with histologic and immunocytochemical observations. During nerve degeneration in the distal segments of crushed nerves, a significant reduction in AR activity was detected. At 5 and 14 days, coincident with Schwann cell proliferation, enzyme activity decreased by nearly two- and fourfold, respectively. Although activity of AR increased by 28 days during nerve regeneration, it was not restored to normal levels at 35 days. Similar reductions were observed with the immunoblotting of the enzyme. Quantitative analysis of immunogold labelling on electron micrographs confirmed that proliferating as well as remyelinating Schwann cells contained reduced gold particle density compared to Schwann cells of noncrushed myelinated fibers. Immunoblots of P0, a marker for the degree of Schwann cell differentiation or myelination, showed that the temporal sequence of changes in P0 paralleled that of AR. Thus expression of AR is a function of differentiated or mature Schwann cells. The putative volume regulatory role of AR in Schwann cells may become superfluous during Wallerian degeneration.

Albumins↗

PubMed1991

Response of the axon and barrier endothelium to experimental allergic neuritis induced by autoreactive T cell lines.

Experimental allergic neuritis was induced in Lewis rats by inoculation with autoreactive T cell lines sensitized to residue 57-81 of P2 myelin protein. Control rats received cells derived from immunization to complete Freund's adjuvant alone. Endoneurial fluid pressure (EFP) was measured in both sciatic nerves at 0, 3, 5, 7, 9, and 11 days post-inoculation (PI). The temporal evolution of inflammatory disease was studied by correlating EFP with a morphometric analysis of the nerve microenvironment and with electron microscopic observations. Both edema, as evidenced by increased endoneurial extracellular space, and inflammation paralleled the time course of the EFP increase, reaching peak values at 7 days PI and declining to near-normal values after 11 days. Wallerian degeneration was detectable at 7 days and increased 9 days after inoculation. Axonal damage appeared at the height of the inflammatory process, when edema and increased EFP were maximal. Evidence of demyelination was apparent by 7 days and persisted through 11 days. The onset of edema was associated with changes in venular endothelial cells which tended to lose their normal scaphoid appearance and assumed rhomboid configurations reminiscent of high endothelial venules. At that point, the barrier endothelium was visibly disrupted with the loss of tight junctions and separation of adjacent cells. Specific cell-cell interactions took place between endothelial cells and infiltrating leukocytes as they immigrated into the endoneurial compartment. There was evidence of altered perineurial permeability with fibrin deposition and leukocyte infiltration between the layers of the perineurial sheath.

Animals↗

PubMed1991

Fine-structural localization of aldose reductase and ouabain-sensitive, K(+)-dependent p-nitro-phenylphosphatase in rat peripheral nerve.

Aldose reductase was visualized by light and electron microscopy using a goat anti-rat antibody with immunoperoxidase and immunogold, respectively. Ouabain-sensitive, K(+)-dependent, p-nitro-phenylphosphatase, a component of (Na+, K+)-ATPase, was localized at the electron microscopic level by enzyme histochemistry using p-nitro-phenylphosphate as substrate. In peripheral nerve, spinal ganglia and roots, the Schwann cell of myelinated fibers was the principal site of aldose reductase localization. Immunostaining was intense in the paranodal region and the Schmidt-Lanterman clefts as well as in cytoplasm of the terminal expansions of paranodal myelin lamellae and the nodal microvilli. Schwann cell cytoplasm of unmyelinated fibers were faintly labelled. Endoneurial vessel endothelia, pericytes and perineurium failed to bind appreciable amounts of aldose reductase antibody. However, mast cell granules bound antibody strongly. In contrast, p-nitro-phenylphosphatase reaction product was detected in the nodal axolemma, terminal loops of Schwann cell cytoplasm and the innermost layer of perineurial cells. In endothelial cells, reaction product was localized on either the luminal or abluminal, or on both luminal and abluminal plasmalemma. Endothelial vesicular profiles were often loaded with reaction product. Occasional staining of myelin and axonal organelles was noted. Mast cells lacked reaction product.

4-Nitrophenylphosphatase↗

PubMed1991

Cellular pathology of the nerve microenvironment in galactose intoxication.

The effect of chronic hyperglycemia and polyol pathway activation on the Schwann cell has not been resolved although injury to this cell has long been suspected in diabetic neuropathy. Hyperglycemia, resulting from galactose intoxication of four months duration, induces dose-dependent accumulations of endoneurial fluid sodium and chloride that are linked to polyol pathway activity and associated with dose-dependent increases in sciatic nerve water content, endoneurial fluid pressure and (Na+, K+)-ATPase activity. In order to understand the impact of these changes on the nerve microenvironment, cellular elements of the endoneurium were quantitatively and qualitatively assessed in rats receiving 0%, 10%, 20% or 40% galactose diets. After four months of galactose intoxication, dose-dependent changes in the size distribution of myelinated nerve fibers were apparent. A shift in size-frequency histograms of galactose-intoxicated animals towards smaller fibers was accompanied by a decrease in axon diameter and the volume fraction ratio of axon to myelinated nerve fibers. In the sciatic nerve of all 40% galactose-fed rats examined by electron microscopy, Schwann cells of myelinated fibers showed both reactive and degenerative changes. Demyelination was preceded by splitting at the intraperiod line. Remyelination was identified by axons with disproportionately thin myelin sheaths. Axonal dystrophy and degeneration were infrequently seen, but there was axonal regeneration. Dose-dependent increases in mast cell number were observed with degranulation apparent in rats receiving 20% and 40% galactose. Endothelial cell number and basal lamina thickness were increased in the endoneurial vessels of galactose-intoxicated rats. Increased cytoplasmic area and degenerative changes in pericytes were also noted. These observations indicate that significant morphologic changes accompany the hyperosmotic imbalance resulting from galactose intoxication of four months duration. Schwann cell injury and demyelination are present in a disorder linked to polyol metabolism since aldose reductase, the anabolic enzyme of the polyol pathway, is localized to this myelin-forming cell.

Animals↗

PubMed1991

Comparative histology of experimental allergic neuritis induced with minimum length neuritogenic peptides by adoptive transfer with sensitized cells or direct sensitization.

Using synthetic peptides representing specific regions of the bovine myelin protein P2, the minimum peptide length requirement for the T-cell epitope necessary for successful production of experimental allergic neuritis (EAN) has been shown to involve residues 61-70 of the P2 protein. In this study, morphometric analysis was used to compare the histologic changes in sciatic nerves of Lewis rats after disease was induced by P2 specific neuritogenic T-cell lines (P(2)3) or, alternatively, by direct inoculation of synthetic peptides representing residues 60-70 or 61-70 of the P2 protein sequence. Inoculation with cell line P(2)3 stimulated with residue 61-70 failed to elicit demyelination in sciatic nerves. However, cells stimulated with residue 60-70 produced inflammation, endoneurial edema, mild demyelination and axonal degeneration within seven days. In contrast, disease induced with either peptide by direct sensitization was more severe. Morphometric analysis revealed that inflammation was most severe in animals sensitized to the decapeptide. In the sciatic nerve, axonal degeneration was proportional in frequency to the extent of inflammation. Inflammation was especially intense in spinal roots with extensive destruction of axons including unmyelinated fibers. Spinal root changes were associated with Wallerian degeneration in the posterior white matter tracts of the spinal cord and were apparently secondary to endoneurial inflammation. Disruption of the blood-nerve-barrier (BNB), evident as physical separation of endothelial cells in association with severe perivascular inflammation, was observed.

Animals↗

PubMed1991

Subperineurial demyelination associated with reduced nerve blood flow and oxygen tension after epineurial vascular stripping.

Using laser Doppler measurements of nerve blood flow and electron microscopy, we determined that removal of the vasa nervorum from the surface of rat peripheral nerve results in an immediate 58.4% +/- (SD) 12.6% reduction in nerve blood flow (p less than 0.017) and subsequent subperineurial demyelination. To further assess the role of ischemia in demyelination, a second group of Sprague-Dawley rats (250 to 300 gm) was anesthetized and oxygen tensions were recorded with platinum microelectrodes in the tibial epineurial and endoneurial spaces before and 30 minutes after epineurial devascularization. Normal epineurial oxygen tension was 40.4 +/- (SD) 6.5 mm Hg before devascularization and 26.3 +/- 12.3 mm Hg after (p less than 0.012). Normal endoneurial oxygen tension was 22.9 +/- 6.0 mm Hg before devascularization and 14.3 +/- 5.4 mm Hg after (p less than 0.003). The topography of nerve fiber injury in this experimental model is identical with the changes induced in the sciatic nerve by circumferential compression at 30 mm Hg which is also thought to impede epineurial circulation. This subperineurial pattern of demyelination and axonal degeneration is associated with experimental interference with the epineurial circulation and may be contrasted with the central fascicular degeneration caused by microsphere embolization of the vasa nervorum via the common iliac artery. The data suggest that ischemia is the mechanism for subperineurial fiber injury after epineurial devascularization and highlight the importance of the transperineurial vessels which connect the epineurial anastomotic circulation and endoneurial capillary network.

Animals↗

PubMed1990

New minimum length requirement for a T cell epitope for experimental allergic neuritis.

The bovine P2 protein induces experimental allergic neuritis (EAN) in Lewis rats. Using synthetic peptides representing regions of the P2 protein sequence and P2-specific neuritogenic T cell lines, we have demonstrated that the minimum peptide length requirement for the T cell epitope for EAN is residues 61-70 of the P2 protein having the sequence EISFKLGQEF. Adding a threonine at the NH2 terminus of this peptide reproduces residues 60-70 of the P2 protein sequence and significantly enhances the neuritogenic capability of this peptide.

Animals↗

PubMed1990

Role of the blood-nerve barrier in experimental nerve edema.

Nerve edema is a common response to the nerve injury seen in many peripheral neuropathies and is an important component of Wallerian degeneration. However, independent pathologic effects of nerve edema that aggravate or induce nerve injury extend the role of edema beyond that of an epiphenomenon of injury. New insights into the mechanism and impact of nerve edema come largely from animal models. In the following review, we discuss the cause and consequences of nerve edema with particular reference to endoneurial fluid pressure and its relevance to the nerve microenvironment. Experimental models of nerve edema include conditions with increased vascular permeability such as lead poisoning, experimental allergic neuritis, and murine globoid leukodystrophy. Increased perineurial permeability induced by local anesthetics and neurolytic drugs can also induce nerve edema sufficient to increase endoneurial fluid pressure. Both perineurial and vascular permeability are increased after damage induced by crush, freeze, or laser injury. One of the most important forms of nerve edema is induced by external compression; the significance of this change is that edema has local compressive effects that persist after the external pressure has been relaxed. Nerve edema and increased endoneurial fluid pressure also occur in conditions in which vascular permeability appears to be unchanged such as experimental diabetic neuropathy and in hexachlorophene intoxication. In both of these conditions, reduced nerve blood flow has been demonstrated in rats and is viewed as a consequence of increased endoneurial fluid pressure. Whatever its mechanism, endoneurial edema has important structural and functional consequences for nerve fibers. A clear understanding of the underlying pathology of the nerve microenvironment may provide useful insights into treatment of clinical neuropathies.

Animals↗

PubMed1989

Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by CD4+ T cells reactive with myelin basic protein (MBP). Rats were rendered resistant to the induction of EAE by vaccination with synthetic peptides corresponding to idiotypic determinants of the beta chain VDJ region and J alpha regions of the T cell receptor (TCR) that are conserved among encephalitogenic T cells. These findings demonstrate the utility of TCR peptide vaccination for modulating the activity of autoreactive T cells and represent a general therapeutic approach for T cell-mediated pathogenesis.

Amino Acid Sequence↗

PubMed1989

Peripheral nerve pathological findings in familial amyloid polyneuropathy: a correlative study of proximal sciatic nerve and sural nerve lesions.

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased-fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a space-occupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.

Adult↗

PubMed1989

Pressure increase in the dorsal root ganglion following mechanical compression. Closed compartment syndrome in nerve roots.

Spinal nerve roots including the dorsal root ganglion (DRG) often are mechanically deformed in connection with degenerative and traumatic conditions of the spine. However, the pathophysiology underlying various functional changes, including pain production, in such conditions is incompletely known. In this study, the tissue fluid pressure in the DRG of L5 nerve roots of rats was measured before and after compression. Normal values were found to be 3.7 +/- 0.3 cm H2O (2.7 +/- 0.2 mm Hg). After mechanical compression, the endoneurial fluid pressure in the ganglia rose to 9.6 +/- 1.7 cmk H2O (7.1 +/- 1.2 mm Hg) (P less than 0.001). Histologic examination revealed edema and haemorrhage in the endoneurial space of the DRG. Pressure increase in the DRG as a result of mechanical deformation by, for example, a herniated disc might be expected to reduce blood flow to the sensory nerve cell bodies in the DRG. This may be a mechanism underlying the production of nerve root pain, which previously has not been described.

Animals↗

PubMed1989

Myoneural necrosis following high-frequency electrical stimulation of the cast-immobilized rabbit hindlimb.

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

Animals↗

PubMed1989

Quantitative histologic analysis of local anesthetic-induced injury to rat sciatic nerve.

Quantitative measurements of endoneurial edema, cytoplasmic lipid droplets, nerve fiber injury and Schwann cell damage were used to elucidate the pathogenesis of local anesthetic-induced injury to sciatic nerve in the rat. All histopathologic measurements were conducted on rat sciatic nerves removed at 48 hr after the extraneural injection of one of three concentrations of the local anesthetic 2-chloroprocaine, procaine, etidocaine or lidocaine. All four drugs produced a concentration-dependent increase in every measure of injury assessed by light microscopy with computer-assisted morphometry of transverse 1-mu thick sections. Edema, lipid inclusions and fiber injury were seen predominantly in the subperineurial region and to a lesser degree in the central areas of nerve fascicles. Quantitative electron microscopic evaluation of Schwann cell injury indicated that the Schwann cells of unmyelinated fibers were more likely to undergo lysis after exposure to local anesthetics, whereas those of myelinated fibers were more likely to accumulate cytoplasmic lipid droplets. These quantitative data on the specificity of the regional distribution of nerve injury and of Schwann cell effects are consistent with a direct cellular toxicity of the local anesthetics; however, these results do not preclude a role for toxicity mediated indirectly by changes in the endoneurial environment.

Anesthetics, Local↗

PubMed1988

Extracellular fluid conditioned during peripheral nerve regeneration stimulates Schwann cell adhesion, migration and proliferation.

Schwann cell movement and proliferation occur during peripheral nerve regeneration and remyelination. We asked whether soluble factors promoting these activities were present in fluid surrounding rat sciatic nerves regenerating across a 10-mm gap bridged by a silicone tube. In this model, regenerated and remyelinated axons extend across the gap by 28 days following nerve transection and tube implantation. Fluid conditioned by cells participating in nerve regeneration (RCF) was assayed for its ability to promote Schwann cell adhesion, migration and proliferation in vitro. RCFs collected at post-transectional days 1-28 were equally effective in promoting Schwann cell-substratum adhesion. In contrast, the motility-promoting activity of RCF was minimal at 1-2 days following nerve-transection, peaked at 7 days and remained elevated through 21 days. The RCF peak response was 87-fold greater than control. Schwann cell proliferative activity of RCF exhibited peaks of activity at 1 and 14 days post-transection. The biological potency of this fluid for each activity assayed in vitro correlated well with the behavior of Schwann cells chronicled during nerve repair in vivo. These findings suggest that soluble factors promoting Schwann cell adhesion, migration, and proliferation accumulate extracellularly during peripheral nerve regeneration and remyelination.

Animals↗

PubMed1988

Pathology of local anesthetic-induced nerve injury.

Nerve fiber injury and endoneurial edema were induced by the injection of the local anesthetic 2-chloroprocaine, tetracaine, procaine, etidocaine or mepivacaine into the soft tissue and fascia surrounding the sciatic nerve of Sprague-Dawley rats. Light microscopy demonstrated that the perineurial barrier was not mechanically damaged by the surgical procedure but, at 48 h post-injection, perineurial permeability was increased. Previous observations of leakage of horseradish peroxidase and the present report of neutrophils and eosinophils in the endoneurium indicate a disruption of blood-nerve barrier systems. Endoneurial edema was observed in the subperineurial, interstitial and perivascular regions. Axonal degeneration and demyelination occurred; the latter associated with accumulation of large lipid droplets in Schwann cells. Degranulation of mast cells, proliferation of fibroblasts and macrophage activity were noteworthy in affected areas. The findings are remarkable in that this is the first model of endoneurial edema by a neurotoxin which penetrates the perineurium, disrupting barrier system and inducing nerve fiber injury.

Anesthetics, Local↗