The effect of brain implants of Walker 256 carcinosarcoma tumour cells on the integrity of the blood-brain barrier was examined in rats using labelled albumin, horseradish peroxidase and trypan blue. Barrier integrity was intact within 1 hour of implantation but was gradually reduced within the tumour after 3.5 days. This was related to alterations in the fine structure of the tumour capillaries. Dissociated tight junctions were apparent within the tumour centre, but no fenestrated endothelium or gap junctions were observed by electron microscopy.

Animals↗

PubMedDate not supplied

Ultrastructural changes in axons caused by acrylamide above a nerve ligature.

The ultrastructural features of the ascending degeneration produced by acrylamide in peripheral nerves above the point of nerve ligature have been described. Before the onset of signs of axonal degeneration abundant accumulation of smooth endoplasmic reticulum and vesicles occur particularly proximal to nodes of Ranvier, but also in internodal regions. Some mitochondrial accumulations occur distal to nodes of Ranvier. The changes closely resemble those found in axons up to 4 mm above a nerve crush in normal animals and appear to be essentially non-specific in nature. Their significance in relation to the subsequent axonal degeneration can only be guessed at.

Acrylamide↗

PubMedDate not supplied

Comparison between the early changes in isoniazid intoxication and the chromatolytic response to nerve ligation in spinal ganglion cells of the rat.

The early effects of acute isoniazid intoxication and the early responses of the neuron to axotomy have been compared in lumbar spinal ganglion cells in the rat. The cells were studied by light and electron microscopy during the 4 days after a single oral dose (2g/kg) of isoniazid and for four days after application of a tight ligature to the sciatic nerve at the level of the sciatic notch. After axotomy a greater proportion of cells showed changes visible by light and electron microscopy than after INH. Small dark neurons were affected more rapidly and more severely by both insults than the large light cells as evidenced principally by changes in their ribosomal organization. Large light cells showed little response to INH. The first response to axotomy was visible about 12 h after injury. The response to INH began 24 h after the single oral dose. The early cell responses to INH therefore apparently precede axon degeneration which is first seen 72 h later and are thus probably a direct toxic effect.

Animals↗

PubMedDate not supplied

The pattern of recovery of axons in the nervous system of rats following 2,5-hexanediol intoxication: a question of rheology?

Rats have been dosed with 2,5-hexanediol for 48 days and then allowed to recover. The changes in the accumulations of neurofilamentous masses in various pathways in CNS and PNS have been followed by light microscopy over the subsequent 9 weeks. It was found that many CNS pathways allow the argyrophilic masses to pass to their terminals from whence they subsequently disappear, usually over 5-6 weeks. Little or no axonal degeneration is seen where this happens. The same occurs in many peripheral nerves, particularly cranial nerves. However, in many tracts in the spinal cord and in many axons in the longer peripheral nerves, filamentous masses remain and becomes associated with axon degeneration, and, in tracts, gliosis. The importance of paranodal constrictions at nodes of Ranvier which tend to be greater in larger diameter axons is emphasized as a likely mechanism for the axon degeneration which largely took place during the recovery period.

Animals↗

PubMedDate not supplied

The early evolution of neurofilamentous accumulations due to 2,5-hexanediol in the optic pathways of the rat.

Rats were given 2,5-hexanediol in their water for more than 5 weeks. The changes in the optic pathways were studied both qualitatively and quantitatively. Increase in 10-nm filaments within axons was noticeable from 10 days onwards in the superior colliculus and in the brachium of the superior colliculus. From then onwards there was a steady increase in the number of affected axons, and their gross enlargement occurred. The proportion of affected fibres in the brachia was in fact few, but all fibres were of retinotectal origin. Less than half of those in the superior colliculus that were swollen were of retinal origin. Measurement of axon diameter versus myelin sheath thickness showed gross relative thinning of the latter. Axon degeneration did not occur but there was increasing ultrastructural evidence of impairment of transport of organelles both centrifugally and centripetally as the filamentous masses accumulated.

Animals↗

PubMedDate not supplied

The pathokinetics of acrylamide intoxication: a reassessment of the problem.

Acrylamide was given intraperitoneally to rats (30 mg/kg/day, five times/week) for 3 weeks, and the nervous and muscle tissues were examined by conventional methods over 5 weeks. Three striking cellular changes were observed. 1 Scattered degeneration of many Purkinje cells from 5 days onwards. 2 Widespread swelling and argyrophilia of nerve terminals from 10 days in both PNS and CNS. Motor and sensory endings were equally affected in all muscles examined. Synaptic and preterminal swelling also occurred in spinal cord, brain stem, and in certain cerebellar terminals. Degeneration occasionally followed this change, particularly in sensory nerve fibres, but not necessarily. 3 Chromatolysis in spinal ganglion cells and occasionally in anterior horn cells from 7 days onwards before the onset of axonal degeneration. This unique sequence of events is discussed in the light of the metabolic and other changes described by earlier authors.

Acrylamides↗

PubMedDate not supplied

The effects of acrylamide on beta-glucuronidase and acid phosphatase activities in rat sciatic nerve above and below a ligature.

The enzymes beta-glucuronidase and acid phosphatase have been assayed by histochemical and by fluorimetric methods above and below a tightly tied ligature on the rat sciatic nerve over the subsequent 10 days. These findings have been compared with similarly treated animals also given four daily doses of acrylamide (50 mg/kg). The following have been found: 1 during this time, acrylamide at this dose causes slight increases in beta-glucuronidase in untied sciatic nerves, detectable both histochemically and fluorimetrically; 2 below the ligature both enzyme activities were greatly increased and this was slightly reduced in the acrylamide-dosed animals; 3 there was a mild rise in beta-glucuronidase activity in the 1.0 cm above the ligature in undosed animals demonstrable both histochemically and fluorimetrically; 4 that in the acrylamide-dosed animals there was a marked rise in beta-glucuronidase activity both 1.0 cm and 2.0 cm above the ligature which was intensified at 7 days and at 10 days after dosing. This was demonstrated both histochemically and fluorimetrically. These results are discussed in the light of the known sheath cell and axonal responses to acrylamide intoxication.

Acid Phosphatase↗

PubMedDate not supplied

The evolution of intracellular responses to acrylamide in rat spinal ganglion neurons.

Acrylamide (30 mg or 50 mg/kg/day, 5 days each week) was injected intraperitoneally into rats for up to 4 weeks. Lumbar spinal ganglia, spinal cord and lumbrical muscle spindles were examined by light and electron microscopy at various times during this period. The first abnormalities in spinal ganglion neurons were seen at 7 days when an apparent increase in numbers of mitochondria, some being hypertrophic, were found in a few large light cells. This was 10 days before any significant Wallerian degeneration was found in muscle spindle sensory fibres. Mitochondrial changes became more marked with time and were later associated with RER disruption, loss of neurofilaments and peripheral displacement of the nucleus thus mimicking chromatolysis of the axon reaction. All these changes began, however, before axon degeneration. Evidence of increased satellite cell activity was maximal at 21 days. These changes are discussed in the light of the possibility that calcium entry into the cell may be seriously increased early in the intoxication as a direct result of the presence of acrylamide and that many of these cellular features are secondary responses to such an event. Distal degeneration of axons seems likely to be secondary to the perikaryal changes.

Acrylamide↗

PubMedDate not supplied

Evolution of the intracellular changes in neurons caused by trimethyltin.

Rats have been given a single dose of trimethyltin (10 mg/kg) and the intracellular events have been followed particularly in hippocampus, cerebral cortex, cerebellum and spinal ganglion cells. The earliest change visible occurs 12 h after this dose and is found to be dense membrane-bound bodies, probably derived from branching tubulo-vesicular smooth endoplasmic reticulum formations. These occur in close connection with rought endoplasmic reticulum and polyribosomes and appear also to have some association with the Golgi complex. At 24 h there is a general vacuolation of Golgi cisterns and SER membranes, and the membrane-bound dense body formation is greatly increased. SER abnormalities are particularly conspicuous in Purkinje cells. In spinal ganglion cells, while vacuolation of Golgi cisterns is intense, dense bodies are inconspicuous and are replaced by increased autophagosomes, often of great complexity. By 48 h vacuolation of Golgi cisterns has waned, but accumulation of dense bodies and secondary lysosomes has steadily increased. In spinal ganglion cells autophagosomes only are increased as the Golgi vacuolation declines. At later times steady increases of lysosomal dense bodies is seen generally accompanied in hippocampal pyramidal cells and dentate fascia cells by abundant cell death. The suggestion is put forward that the Golgi complex may be the seat of the critical metabolic lesion and disturbances to protein transfer and protein synthesis follow. No explanation for the selective loss of hippocampal h1-5 (CA1-CA4 except Sommer's sector) pyramidal cells and of small dentate fascia neurons can be derived from these conclusions.

Amygdala↗

PubMedDate not supplied

Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells.

A single dose (10 mg/kg) of Adriamycin was given to 23 adult Wistar rats and the spinal ganglia were studied from 6 h to 15 days after. As previously described, this drug results in the appearance of 'clear' areas in the nuclei of rat spinal ganglion cells as seen by light and by electron microscopy. The 'clear' areas become less conspicuous during the week before the onset of cytoplasmic degeneration. In addition, nucleolar changes become increasingly evident with time after injection. Fibrillar centres enlarge and nucleolar segregation is present from 24 h onwards, although the latter is invariably partial and more readily seen with the electron microscope. Nucleolar fragmentation is seen more frequently from 3 days onwards and nucleolar enlargement is common from 6 days. Early cytoplasmic abnormalities are associated with pronounced loss of Nissl substance. Adriamycin must bind extensively to nuclear DNA in spinal ganglion cells, causing the 'cleared' nuclear areas and the changes in dense chromatin. In addition, the binding of Adriamycin to nucleolar DNA with disturbance to nucleolar functions must be important in producing later cytoplasmic changes that precede cell death. There are thus similarities between the action of Adriamycin on these cells and those of Cisplatin, although in the latter intoxication the nuclear effects are significantly less prominent.

Animals↗

PubMedDate not supplied

Homage to professor Alfred Meyer on his 94th birthday.

Explore the source record for details and available documents.

History, 20th Century↗

PubMedDate not supplied

Persistent mercury in nerve cells 16 years after metallic mercury poisoning.

A male subject, after exposure to mercury metal at work in 1968, developed classical signs of mercurialism from which he made a slow clinical recovery. He subsequently developed psychoneurotic symptoms and became an alcoholic; he never returned to work and died in 1984. No histological changes relevant to mercury intoxication were found in the brain, but staining by Danscher & Schroeder's method for mercury showed many positively staining lysosomal dense bodies in a large proportion of nerve cells, and the presence of mercury was confirmed by elemental X-ray analysis. The mercury content of the brain was increased, much of it being present in colloidal form.

Brain↗