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Biomedical subjects

B G Cragg

Publications and source records attributed to B G Cragg.

At least 19 recordsLinked to original sources
PubMed1986

The effect of maternal thyroidectomy prior to conception on foetal brain development in sheep.

Merino ewes were surgically thyroidectomized, and mated 6 weeks later when their plasma thyroxine (T4) levels were negligible. Their foetuses were delivered by hysterotomy at 52, 71, 84, 98, 125, 140 days gestation or at term (150 days). Despite the very low levels of T4 in maternal plasma, the concentrations of T4 in foetal plasma were not significantly different after 71 days gestation from those of foetuses of sham-operated (control) ewes. Foetal brain and body weights, however, were reduced from 71 days compared to those of foetuses of sham-operated ewes. The foetal brain weights but not the body weights were restored to normal from 125 days to term. In addition to the weights, cell number (DNA) and cell size (protein:DNA ratio) appeared to be normal in the neonatal brain at parturition and this was confirmed by histological examination of the brains. Thus lack of maternal thyroid hormones in early pregnancy may cause a reduction in brain and body growth in the foetus which, in the case of the brain, appears to be restored to normal after the onset of foetal thyroid function.

Animals↗
PubMed1984

Organic lead and histological parameters of brain development.

Relatively little work has been done on the structural effects of organic lead in the central nervous system (CNS), although this form of lead may be a significant fraction of total brain lead. We tested a number of easily measured light-histological parameters of neuronal development in rats for sensitivity to (a) normal growth between 18 and 28 days of life and (b) the effect of weekly injections of tetramethyl lead (TML), administered from 1 week after conception until post-natal day 6. Several of the histological parameters were found to be sensitive to normal growth, but none showed any effect of organic lead treatment. This was despite a small but significant decrease in brain weight, and a significant increase in body/brain weight ratio, with tetramethyl lead treatment. The body/brain weight ratio was the parameter most sensitive to tetramethyl lead treatment. Possible reasons for the disparity between weight and histological parameters are discussed, with reference to previous workers' findings concerning the effects of organic lead on the development of myelin in the CNS and the availability of organic lead to brain tissue.

Age Factors↗
PubMed1984

Blood-brain barrier dysfunction in thiamine-deficient, alcohol-treated rats.

Rats maintained on a thiamine-deficient diet for 38 days loss weight and showed neurological symptoms. The PA value, representing the permeability of the blood-brain barrier to 14C-sucrose, was significantly increased whether urethane or ethanol was used as anaesthetic. This increase was prevented by giving rats on the same diet injections of thiamine twice weekly. Barrier function was normalised by injecting thiamine into deficient rats for just 3 days before biopsy. The brains of the thiamine-deficient rats were stained by the Fink-Heimer method but showed no degenerating axons except for silver grains in the glomeruli of the olfactory bulb. Other rats were maintained on the same diet for 38 days and additionally exposed to ethanol vapour for 16 h per day. This resulted in a similar loss of weight but a greater leakage of the blood-brain barrier. The latter was normalised by a thiamine injection only 24 h before biopsy, but was not reduced by withdrawal of ethanol for 3 days before biopsy. Axonal degeneration was present in the olfactory glomeruli. However, no lesions or extravasated blood cells were seen in any brains, there was no change in brain water indicative of oedema and no degeneration in retina, distal peripheral nerves or leg muscles. The relation of these and other experimental findings to alcohol-related brain damage is considered.

Animals↗
PubMed1984

Restoration of brain growth in fetal sheep after iodized oil administration to pregnant iodine-deficient ewes.

Iodized oil was administered as a single intramuscular injection to pregnant iodine-deficient ewes at 100 days gestation and the subsequent growth of their fetuses compared with that of fetuses of severely iodine-deficient ewes and of iodine-replete ewes, all of which were fed the same low-iodine diet. The administered iodine produced a remarkable improvement in thyroid function and physical appearance of the fetuses, accompanied by an increase in brain growth and to a lesser extent in body growth, which at 140 days was only slightly (but significantly) less than that of the controls. There was restoration of the number of cells (DNA) and myelination (cholesterol/DNA) in the cerebellum and cerebral hemispheres which suggests a catch-up of neuroblast development during pregnancy. Histological examination, however, revealed that counts of synapses (density) in the cerebral cortex after iodized oil were still less than those of the control fetal brains. The relevance of these findings to the effects of iodine deficiency on human brain development is discussed.

Animals↗
PubMed1984

Alcohol withdrawal causes a loss of cerebellar Purkinje cells in mice.

Mice received a liquid diet containing alcohol for 4 months, after which half of them were sacrificed and the others given a 4-month recovery period before being sacrificed. They were compared with similar mice receiving the diet with alcohol replaced isocalorically by sucrose. No damage was detected in the cerebellum during alcohol consumption, but the number of Purkinje cells was significantly reduced in the recovery period. The experiment was repeated twice with mice consuming a normal diet but exposed to alcohol vapor. The first group was exposed to alcohol vapor 24 hr/day for 3 weeks and then given alternating 1-week periods of recovery and exposure 24 hr/day until a total of 6 weeks of exposure to alcohol vapor and 4 one-week recovery periods had been experienced. They were compared with similar mice exposed to alcohol vapor 24 hr/day for 6 weeks without a recovery period. The second group was exposed to alcohol vapor 9 hr/day for 3 weeks, when part of the group was given a 3-week recovery period. In both experiments, damage was not detected in the cerebellum during alcohol exposure, but in mice withdrawn from alcohol, the number of Purkinje cells was reduced and qualitative evidence of neuronal degeneration was found with a silver stain. In a further group of mice, exposure to alcohol vapor was tapered off gradually, and no evidence of neuronal loss was found. Indications in the literature that withdrawal from alcohol can cause brain damage are briefly reviewed.

Aerosols↗
PubMed1983

Chronic consumption of alcohol by adult mice: effect on hippocampal cells and synapses.

For 4 months C57 black mice were fed a nutritionally complete diet containing 9% alcohol or isocaloric sucrose and killed then or after 4 months recovery on standard food pellets. The number of cells in a thin plastic section of hippocampus was unchanged in field CA1 by alcohol exposure but was reduced 9% during withdrawal from alcohol. Electron microscopy was used to count synapses among the basal dendrites and no significant change was found in any treatment group. The spine heads were measured and found to be smaller in the alcohol group than in the sucrose group; many of the spines (in the alcohol group) were too small to be visible with the light microscope.

Alcoholism↗
PubMed1982

The peripheral and central changes resulting from cutting or crushing the afferent nerve supply to the whiskers.

In neonatal rats, crushing or cutting the infraorbital nerve, the sensory nerve supply to the whiskers, has been found to prevent cortical barrel formation. However, both procedures are followed by regeneration of one-third to one-half of the nerve fibres and reinnervation of the whiskers. By counting fibres in individual whisker follicle nerves, it has been shown that 29-67% (mean 45%) of the myelinated fibres regenerate to the whiskers after a crush compared to 24-56% (mean 39%) after a cut. Further differences between the crush and cut lesions were indicated by studies on the time course of regeneration. Counts of the regenerating fibres at various ages as well as recordings of cortical evoked potentials in normal, nerve-crushed and nerve-cut animals showed that recovery was 3-4 days earlier in the nerve-crushed, compared with the nerve-cut animals. In normal and nerve-crushed animals the evoked potential was first detectable 2-3 days after birth while the response after nerve cut could not be recorded until day 7. Even after 60 days the amplitude of responses on both crushed and cut pathways was only about one-third of normal, while the latency was prolonged (normal 5.8 +/- 0.25 ms, crush 6.5 +/- 0.26 ms, cut 7.7 +/- 0.67 ms). Central changes occurring as a result of nerve cut or crush have been studied by microelectrode recordings from the trigeminal nucleus (the first synaptic level) and the somatosensory cortex. These also indicate clearly the greater severity of the cut lesion. Thus, in crushed animals, all levels of the trigeminal nucleus as well as the cortex show only minor modifications. The whiskers occupy the same total area and responses from all whiskers are present at their normal sites. However, after nerve cut, the responses from both the trigeminal nucleus and cortex show clear abnormalities. The total whisker area is reduced with a concomitant expansion of responses from the nose, check, lower jaw, and whiskers by the eye and ear. In addition, only one-third to one-half of the whiskers give responses. The site of these abnormalities is localized to the trigeminal nucleus since all whiskers show innervation in the peripheral nerve. It is suggested that the longer recovery time as well as the reduced accuracy of reinnervation may contribute to the poorer central recovery after a nerve cut.

Afferent Pathways↗
PubMed1980

Experimental animal model for mucopolysaccharidosis: suramin-induced glycosaminoglycan and sphingolipid accumulation in the rat.

Intracerebral injection of the trypanocidal drug suramin in rats caused the formation of membranous neuronal and neuroglial inclusions. Here we show that intravenous administration suramin, 500 mg/kg, to 2-month-old rats causes a 5- to 8-fold increase of glycosaminoglycan concentration in the liver within 10 days and a 6-fold increase in urinary glycosaminoglycan excertion. The excess glycosaminoglycans consist of heparan sulfate and dermatan sulfate. Intracerebral injection of 250 micrograms of suramin results in a small increase of glycosaminoglycan and larger increase of ganglioside GM2, GM3, and GD3 concentrations in the treated region of the brain. The activities of the lysosomal enzymes iduronate sulfatase, beta-glucuronidase, and hyaluronidase in the liver of the suramin-treated mature rats were consistently decreased, whereas those of alpha-L-iduronidase, heparan N-sulfatase, arylsulfatase B, and others were considerably increased. The activity of iduronate sulfatase was completely inhibited in vitro by suramin at concentrations of 50 microM or higher. The activity of beta-glucuronidase was also strongly inhibited by low concentrations of suramin, but this inhibition was partially decreased at higher concentrations of the drug. The inhibition of both enzymes by suramin was noncompetitive. The suramin-treated rat may be a useful experimental animal model of mucopolysaccharidosis.

Age Factors↗
PubMed1979

The effect of destroying the whisker follicles in mice on the sensory nerve, the thalamocortical radiation and cortical barrel development.

Electrolytic destruction of whisker follicles in mice on the day of birth has been found to cause degeneration in the sensory nerve fibres supplying the follicles. The severity of the degeneration has been assessed in animals between 2 and 20 days old by counting the total number of myelinated fibres in the maxillary nerves on both normal and lesioned sides. The degeneration is apparent after 2 days and by 20 days the nerve on the lesioned side contains only 38% of the normal fibre content. This degeneration has also been shown to involve the trigeminal root, central to the ganglion. In addition, the lesioning procedure modifies the terminations of thalamocortical fibres in the barrel region of the sensory cortex. These terminations are normally in clusters, each corresponding to a barrel, but, after lesioning the follicles, the terminals appear to be evenly distributed in layer IV and cortical barrel structures no longer develop. In postnatal mice, electrolytic destruction of whisker follicles had less effect upon maxillary nerve fibres and cortical barrels. The number of myelinated axons surviving until day 20 increased progressively with later lesioning to reach nearly 80% of the control level when lesions were made on day 10. Cortical barrels became secure earlier than the maxillary nerve, for a normal number of cortical barrels was present at day 12 when follicles were destroyed on day 4. The implications of these results for the formation of cortical barrels is discussed.

Animals↗
PubMed1976

Ultrastructural features of human cerebral cortex.

Neuronal and glial elements have been examined in the temporal or frontal cortex of four brains with normal parenchyma. The identifying features recognized in animal brains have been found valid in human cortex for stellate and pyramidal neurons and their dendrites, spines, synapses, initial segments of axons, nodes of Ranvier and axon terminals; also for astrocytes, oligodendrocytes of various electron densities, pericytes, blood vessels and basement lamina, and for the relation of subarachnoid space to arterioles. However, most microglial cells have unexpectedly sparse and pale cytoplasm with few organelles, and the distribution of glial nuclear chromatin is not entirely in accordance with that described in animal brains. Fusiform neurons have been identified, and their cytoplasm resembles that of stellate cells. Peculiarities of human cortex include a nuclear inclusion that is present in stellate neurons only. Two neuronal cell-body profiles were myelinated, and a blood capillary was seen to penetrate a neuron. Somatic spines were found occasionally with or without synapses. Ribosomes can be present in axons, espicially at nodes of Ranvier, and a small portion of axon terminals contain a variety of dense bodies of which some are derived from mitochondria. Endoplasmic reticulum can occur in a compressed stack in neurons, and an unusual vesicular organelle has been seen in dendrites, axons and somata. Astrocytes as well as oligodendrocytes and occasional microglial cells act as satellites to neurons, and the exchange of a membrane-bound body between a neuron and asatellite glial cell is illustrated. Some dark pycnotic neurons were present, and it was remarkable that a closely apposed neuron could be entirely normal. These findings are compared with published descriptions of cortical ultrastructure in the brains of laboratory animals.

Animals↗
PubMed1975

The development of synapses in the visual system of the cat.

Synapses have been counted by electron microscopy and neurones by light microscopy through the depth of the visual cortex in a series of cats from 37 days gestation to adulthood. A few definite synapses are present as early as three weeks before birth, but there is then a latent period of four weeks before synapses increase rapidly in number 8-37 days after birth. The synapses occur just above and just below the cell plate at first, but in the adult cat they become evenly distributed in the depth of the cortex. The gradual separation of neurones by neuropil during development precedes a parallel increase in the density of synapses by about one week. The average number of synapses associated with one neurone rises to a peak of about 13,000 at seven weeks after birth. The densities of synapses and of neurones subsequently fall to slightly lower values in adult cats as the glial cells continue to develop. The timing of synaptic development in the visual cortex has been compared quantitatively with that in the L. G. N. and qualitatively with synaptogenesis in the retina. Synapses develop in the L. G. N. and cortex in a parallel fashion, and the L. G. N. precedes the cortex by a short interval of about two days. In the cell plate of the retina a few receptor synapses are present nine days before birth. Inner plexiform synapses are aslo present at this time, but ribbon-containing synapses do not appear until birth. Very few receptors possess outer segments with discs at birth, but five days later disc-bearing outer segments have developed. Thus synaptic development starts before afferent impulses can enter the visual system, but the main increase in synapses in the L. G. N. and cortex takes place four weeks after the start of synapse formation while the visual system is being used.

Age Factors↗
PubMed1975

The density of synapses and neurons in normal, mentally defective ageing human brains.

The densities of synapses and neurons were measured in 7 neurosurgical specimens of cerebral cortex, regarded as normal controls. The average result was 6 times 10-11 synapses/cm3, 15-6 times 10-6 neurons/cm3, and 38,000 synapses per neuron. Specimens of frontal and temporal cortex from 7 ageing brains (68 to 89 years) gave closely similar counts of neurons and synapses. Seven specimens from 3 severely retarded brains gave similar counts of neurons and slightly higher counts of synapses. A deficit of synaptic development is thus not a necessarre discussed.

Adolescent↗