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Biomedical subjects

J B Cavanagh

Publications and source records attributed to J B Cavanagh.

At least 55 records · Page 3Linked to original sources
PubMed1986

The axon reaction in spinal ganglion neurons of acrylamide-treated rats.

Rats were given acrylamide in doses of either 30 or 50 mg/kg (5 days each week) for up to 3 weeks and killed at weekly intervals. The right sciatic nerve was tied tightly at the level of the major trochanter 4 days before killing the animals by perfusion fixation when ipsilateral and contralateral sensory ganglia (L5 and L6) were removed. The effects on neuronal perikarya of axotomy alone, of acrylamide alone and of these combined were studied by light and electron microscopy. The responses to axotomy and to acrylamide intoxication shared certain features, namely peripheral Nissl substance and to a lesser degree nuclear eccentricity, nucleolemmal crenation and mitochondrial enlargement. Neurofilament loss was present only with acrylamide. In combined axotomy and acrylamide all these five features were prominent. These findings indicate firstly that the individual responses to axotomy and to acrylamide, while sharing several features, are subtly different and secondly that acrylamide appears to impede the vital neuronal responses directed towards repair of the axon.

Acrylamide↗
PubMed1986

The effects of cisplatin on rat spinal ganglia: a study by light and electron microscopy and by morphometry.

Cisplatin given in doses of 0.5-2 mg to Wistar and to Sprague-Dawley rats produced nucleolar segregation of the dense fibrillar from the granular component in spinal root ganglion cells. The nucleolar segregation, found to the same extent in large and small neurons, was confirmed by specific silver staining and by electron microscopy. After repeated doses of 1 mg or 0.5 mg, up to 40% of affected nucleoli were observed by light microscopy. Focal clearing of the nucleoplasm of nuclei also occurred. Disorganisation of ribosomes was found in more severely intoxicated animals, especially in large light cells with shrinkage of the Nissl substance and apparent increase in neurofilaments, the latter occasionally distending the initial segment of the axon, but never extending further. Hypertrophy of the satellite cells with increase in the perineuronal intercellular spaces, often associated with irregular, scalloped nuclear and cell outlines, suggested that neuron shrinkage had occurred. This was confirmed by morphometry and marked alterations were found in nucleolar-to-nuclear and nucleolar-to-cell diameter ratios, nuclear and cell diameters were also somewhat reduced without change in the nucleus-to-cell ratios. Peripheral sensory nerve degeneration was not seen, and the animals died from non-neural causes. The probable role of these events in the production of sensory neuropathy is discussed.

Animals↗
PubMed1985

Morphometric effects of vincristine on nerve regeneration in the rat.

Administration of vincristine (200, 100 or 50 micrograms/kg/week) for 6 months during regeneration of the sciatic nerve after crush injury caused a dose-dependent reduction in nerve fibre size and failure of removal of myelin debris. Successfully regenerating neurites showed an unusual amount of shape distortion. The ratio of myelin sheath thickness to axon circumference was reduced, but the ratio of myelin sheath thickness to axon area was normal. Microtubule concentration was diminished in axons, but neurofilament density was unaffected. Unmyelinated axons were reduced in number but their axon diameter distribution was not affected. Fibres on the non-crushed side appeared normal. The toxicity of vincristine to regenerating nerves is probably related to increased blood-nerve permeability occurring both at the site of crush and along the degenerating nerve.

Animals↗
PubMed1984

The problems of neurons with long axons.

Neurons with long axons are unique among cells in having to maintain a very large area of membrane. In this respect they have problems in common with red cells: the latter are separated from the source of their metabolites in time, the former by distance. In equilibrium, maintenance mechanisms are adequate; but in conditions of energy deprivation or deprivation of antioxidant substances such as glutathione and alpha-tocopherol, or when the transport of materials within the neuron is physically obstructed, the system may break down and the longest fibres will always suffer first. The problems are logistical, just as are those of red cells. The association between red-cell disease and neuropathy is not entirely fortuitous.

Axons↗
PubMed1984

Effects of acrylamide and other sulfhydryl compounds in vivo and in vitro on staining of motor nerve terminals by the zinc iodide-osmium technique.

The zinc iodide-osmium technique blackens motor nerve terminals by selectively staining synaptic vesicles. Intraperitoneal injections of acrylamide (30 mg/kg/day, 5 times each week) cause inhibition of staining by this technique so that approximately one third of the end-plates in rat sternocostalis muscle are unstained after 24 hours, and by 17 days more than 70% are unstained. This is not associated with nerve fiber degeneration. A similar inhibition of staining can also be shown after prior incubation of the sternocostalis muscle in 4 mM acrylamide in oxygenated Ringer's solution. Intraperitoneal injection of the thiol group blocker N-ethylmaleimide also causes marked inhibition of staining of motor end-plates by this method. Dithiothreitol, which prevents the oxidation of thiol groups, will partly prevent the inhibition of staining by both acrylamide and N-ethylmaleimide, when given in vivo.

Acrylamide↗
PubMed1984

Effects of acrylamide and some other sulfhydryl reagents on spontaneous and pathologically induced terminal sprouting from motor end-plates.

The innervation of the normal rat sternocostalis muscle exhibits a constant low level of short spontaneous terminal sprouts visible in zinc iodide-osmium (ZIO) and in methylene blue-stained preparations. Acrylamide inhibits these spontaneous sprouts in a dose-dependent manner. This inhibition is mimicked by N-ethylmaleimide (a sulfhydryl group blocking agent) and can be nullified when acrylamide is given after the sulfhydryl group protecting agent, dithiothreitol (DTT). This could not be reversed by giving DTT 3 hours after acrylamide. Furthermore, when given alone DTT increases the level of spontaneous terminal sprouting seen in ZIO and in methylene blue-stained preparations. These findings suggest that the binding of acrylamide to sulfhydryl groups is involved in the inhibitory process. Acrylamide also reduces the number and length of the reactionary terminal sprouts, seen in ZIO and in methylene blue-stained preparations, that follow partial denervation or local injection of botulinum toxin. These inhibitory effects are long-lasting; recovery still has not fully occurred 4 weeks after a single dose of acrylamide (50 mg/kg). The roles of glutathione and other sulfhydryl components of axons are discussed in relation to the mechanism of acrylamide neurotoxicity.

Acrylamide↗
PubMed1984

Changes in terminal sprout formation in rat sternocostalis muscle during chronic intoxication with 2,5 hexanedione.

Qualitative and quantitative morphological studies of the sternocostalis muscle innervation were made on rats chronically intoxicated with 2,5 hexanedione (2,5 HD) using the zinc iodide-osmium (ZIO) technique. Two distinct phases were seen in the events at the motor endplate. First, the number of motor endplates forming spontaneous terminal sprouts was found to increase linearly with time and, from the third week onward, the sprouts appeared to become progressively elongated. This latter change was associated with the appearance of swollen axons within intramuscular nerve bundles. Second, from the sixth week onward, wallerian degeneration of nerve fibers was seen and terminal sprouts began to make new arborizations on muscle fibers. By the eighth week, this occurred in as many as 66% of the rats, and collateral sprouting was also observed at this time. The occurrence of increased spontaneous terminal sprouting due to altered neuromuscular function is discussed in the light of axonal changes resulting from neurofilament accumulation following 2,5 HD intoxication.

Animals↗
PubMed1984

The effects of chronic isoniazid intoxication on motor end plate sprouting in rat sternocostalis muscle and on responses to partial denervation and local botulinum toxin.

Chronic dosing of rats with isoniazid (INH) leads to an increase in the incidence of short "spontaneous" sprouts on motor end plates in the rat sternocostalis muscle. After partial denervation there is a slight increase in terminal sprouting after 1 week of dosing: this changes to a significant decrease from 2 to 6 weeks of dosing. The same is noted after local botulinum toxin injection, and in both conditions sprout length is significantly reduced. In vitro studies show that glutathione, cysteine and cystathionine all increase the incidence of short, "spontaneous" sprouts from end plates, while homocysteine and cystine have no effect. These findings are interpreted in the light of the hypothesis that in INH intoxication there may be a reduction of available axonal glutathione and cysteine due to inhibition of the pyridoxal phosphate-dependent enzymes cystathionine synthetase and cystathioninase .

Animals↗
PubMed1983

The effects of 2,5-hexanedione on axonal regeneration after nerve crush in the rat.

The pattern of recovery of myelinated axons in the posterior tibial nerve after crushing was studied in rats chronically intoxicated with 2,5-hexanedione. It was given for 2 weeks before crushing (200 mg/kg i.p. 5 times a week) or additionally for two further weeks after the nerve crush. Two animals were examined from each group at approximately 1,2,3,4 and 8 weeks later. Return of function in poisoned animals was slower than in the controls. The numbers of regenerating myelinated fibres was severely reduced in poisoned animals up to 4 weeks later, but by 8 weeks the numbers equalled those in the control nerves. Marked impairment of initiation of neurite outgrowth was found, but once begun, axonal growth was comparable to controls and myelination occurred normally. Above the crush for 10 mm, filament-filled axonal swellings were found in poisoned animals accompanied by varying amounts of retrograde axonal degeneration. These findings are discussed in relation to the role of normal neurofilaments in axonal growth and the effects of probably cross-linking of these by 2,5-hexanedione on regenerating neurites.

Animals↗
PubMed1983

Ultrastructural features of the Purkinje cell damage caused by acrylamide in the rat: a new phenomenon in cellular neuropathology.

Dosing rats with acrylamide leads to the formation in Purkinje cells of juxtanuclear clusters of tubular and vesicular smooth endoplastic reticulum (SER). A microtubule organizing centre forms in relation to these clusters and together they appear to move to the cell surface, where protrusions of plasmalemma form, often with overlying synaptic attachments, containing densely packed tubular and vesicular SER membranes. Usually the microtubule organizing centre immediately underlies this. Subsequently, appearances suggest that astroglial intrusions occur internal to the protrusions described above to which the tubulo-vesicular material appears to be transferred. During these events the organization of the cytoplasm of the Purkinje cell is grossly disturbed with apparent loss and disarray of rough endoplasmic reticulum (RER) and of polyribosomes. This temporal sequence of events can be followed after a single dose of acrylamide. In chronically intoxicated animals vacuolation and swelling of dendrites takes place and the Purkinje cell may die after all stages of the cellular transformations have been present. These unique events appear to be confined to Purkinje cells and are considered probably to be the result of a primary disturbance to SER synthesis caused by acrylamide. It is argued that the changes taking place in acrylamide intoxication in neurons that lead to degeneration in long axons are probably of the same general kind.

Acrylamides↗
PubMed1983

Distortions of the nodes of Ranvier from axonal distension by filamentous masses in hexacarbon intoxication.

A study has been made of the structural changes of nodal and paranodal regions of the nodes of Ranvier of peripheral nerves of rats in which marked accumulations of neurofilaments have occurred within axons under the influence of 2,5-hexanediol over 10 weeks. The neurofilamentous masses caused distension of the axon at two points of apparent weakness as they attempted to slide through the axonal constriction at the nodes. Principally, a spiral axonal protrusion pushed into the zone of unattached myelin loops in the proximal paranodal spinous bracelet of Nageotte. This led to a conical widening of the paranodal constriction and considerable attenuation of the overlying myelin. No degeneration of the myelin occurred however. Alternatively, or additionally, a protrusion occurred of the axon at the nodal region which increased the nodal gap width and occasionally compressed and displaced the adjacent distal paranodal constriction which could have led to some obstruction of axoplasmic flow. Swelling of distal paranodal regions occurred later and was usually associated with proximal swelling. It was also accompanied by evidence suggesting transnodal passage of filamentous material. Sometimes, however, striking nodal constriction occurred in association with symmetrical paranodal swelling. These observations suggest that the spiral glial-axonal relationships at nodes of Ranvier are capable of marked deformation that might allow the intra-axonal neurofilamentous masses to move distally. These findings are discussed in relation to the structural features of the paranodal constrictions.

Animals↗
PubMed1983

Cytochemical staining characteristics of peripheral nodes of Ranvier in hexacarbon intoxication.

Changes in the distribution of stainable gap substance and subaxolemmal density at peripheral nodes of Ranvier in hexacarbon-intoxicated rats have been studied by light and electron microscopy. Cupric ion binding to the nodal gap substance was seen in normal nodes as a discrete annulus by the formation with ferrocyanide of Hatchett's Brown reaction product. Staining of osmicated fibres with ferrocyanide ions alone gave a deposit of black reaction product at the subaxolemmal region at nodes of Ranvier. Paranodal distension by neurofilamentous masses and separation of the terminal myelin loops in the early phase of paranodal dilatation produced no change in the distribution of the two kinds of stainable material. Paranodal myelin retraction with increases both in nodal gap width and nodal axon diameter resulted in displacement and attenuation of both stained regions. Axonal protrusion at the nodal region tended only to displace the stained gap substance, but sometimes it resulted in its attenuation. Occasionally loss of subaxolemmal staining was found. The possible functional relevance of these abnormal findings is discussed in relation to changes in conduction in affected nerves.

Animals↗
PubMed1983

Effects of acrylamide and botulinum toxin on horseradish peroxidase labelling of trigeminal motor neurons in the rat.

The extent of neuronal labelling with horseradish peroxidase (HRP) was examined in rat trigeminal motor neurons at various stages of acrylamide intoxication, following HRP uptake by motor nerve endings in the anterior digastric muscle. After 7 days of acrylamide (5 daily injections of 30 mg acrylamide/kg body weight), the pattern of HRP labelling was altered from normal, and this changed pattern persisted without further alteration when survival time and dosage were increased to 14 and 21 days (equivalent to 10 X 30 mg/kg and 15 X 30 mg/kg respectively). Six hours after HRP injection, the number of labelled cells in the ipsilateral trigeminal motor nucleus was reduced in treated animals compared to controls. By 18 hours, cells containing label were present in similar numbers to controls; but by 24 hours, the number in treated animals had fallen again, unlike controls in which labelling remained constant between 6 and 24 hours. At longer intervals, this reduction in labelling continued, but more slowly, so that by 96 hours after HRP injection, numbers of labelled cells were again similar in poisoned and control animals. One and three days after a single intramuscular injection of 0.05 microgram botulinum toxin type A, HRP labelling in the trigeminal motor neurons was unaffected, although at three days after toxin, mild chromatolytic changes could be seen in a few of the neurons.

Acrylamides↗
PubMed1983

Bilateral innervation of the anterior digastric muscle by trigeminal motor neurons.

The locations and numbers of trigeminal motor neurons supplying the anterior digastric muscle in the rat were observed following retrograde transport of horseradish peroxidase. Unilateral injection of horseradish peroxidase into the muscle resulted in bilateral labelling of cells in the ventromedial region of the caudal trigeminal nucleus. The numbers of cells on the contralateral side were consistently lower than those in the ipsilateral nucleus (30 cells compared to 171). Bilateral injection of horseradish peroxidase resulted in higher numbers of cells on both sides than was seen ipsilaterally after unilateral injection: these numbers corresponded roughly to the sum of ipsilateral and contralateral labelled cells after a single injection. The contralateral reaction product survived removal of the opposite muscle and nerve immediately before injection. Ablation of one trigeminal motor nucleus caused degeneration in the opposite nucleus, and some degenerating fibres crossed the mid-line at the level of the motor nucleus, in the bundle of fibres decussating in the dorsal pons.

Animals↗