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Biomedical subjects

D C Rogers

Publications and source records attributed to D C Rogers.

At least 19 recordsLinked to original sources

Photothrombotic lesions of the rat cortex impair acquisition of the water maze.

Photochemical induction of a thrombosis produces lesions of the cortex of reproducible area and depth, and it has been suggested that this may provide a relatively noninvasive model of the human condition of stroke. The cognitive effects of photothrombotic lesions centred at two different positions were assessed in rats using the Morris water maze test for spatial learning and memory, and it was demonstrated that profound deficits in acquisition of this task were produced by bilateral lesions of the frontal cortex. These effects were in the absence of overt motor deficits, and there was no significant correlation between lesion volume and functional deficits. Flunarizine (2 mg/kg) did not attenuate this ischaemic damage and had no effect on the functional deficits. This model has distinct advantages over more invasive global models of ischaemia and may also provide greater understanding of the functional role of the mammalian neocortex.

Animals

Behavioral assessment of the effects of embryonic nigral grafts in marmosets with unilateral 6-OHDA lesions of the nigrostriatal pathway.

Grafts of embryonic nigral tissue were made into the striatum of marmosets (Callithrix jacchus) which had previously received a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal bundle. The grafts comprised injections of cell suspensions prepared from embryonic (74 day) marmoset ventral mesencephalic tissue targeted at multiple striatal sites in the caudate nucleus, the putamen, and the nucleus accumbens on the same side as the initial lesion. A series of behavioral tests was used to assess the monkeys prior to surgery, following the 6-OHDA lesion, and at regular intervals for 6 months after transplantation surgery. Lesioned and grafted (n = 6) or lesion alone (n = 4) monkeys were matched as far as possible with respect to their scores prior to transplantation so that explicit graft-derived recovery could be distinguished from any spontaneous recovery that might occur. Sham-lesioned or unoperated monkeys served as further controls (n = 5). The grafts were functionally effective as measured by a reduction, and in some cases a reversal, of spontaneous, amphetamine- and apomorphine-induced rotation. The reversal of amphetamine-induced rotation correlated with the number of dopaminergic neurons in the grafts visualized by tyrosine hydroxylase immunohistochemistry. Successful use of the hands was restored by the grafts on tasks in which the monkeys reached into tubes to retrieve food. However, functional recovery was not seen on some other behavioral tests. In particular, grafts did not influence ipsilateral biases induced by the lesion, including the position of the head with respect to the rest of the body, hand preference while reaching for food at a conveyor belt, and neglect of contralateral stimuli either at the conveyor belt or of adhesive labels placed around the feet. Indeed, the graft group was impaired compared with the lesion group in the accuracy of reaches at the conveyor belt. Overall, these results indicate that embryonic nigral grafts can yield a partial recovery from the symptoms induced by unilateral nigrostriatal lesions in a primate model of hemiparkinsonism.

Animals

A novel population of tyrosine hydroxylase immunoreactive neurones in the basal forebrain of the common marmoset (Callithrix jacchus).

We have observed in the basal forebrain of the common marmoset a group of neurones which display tyrosine hydroxylase immunoreactivity (THir) with three different polyclonal antibodies and one monoclonal antibody, and which express TH mRNA as shown by in situ hybridization histochemistry. The population of cells is composed of large multipolar neurones and is located predominantly in the substantia innominata and at the ventral, medial and lateral margins of the external segment of the globus pallidus. The cell morphology and the distribution of THir cells corresponds closely to the caudal portion of the nucleus basalis of Meynert. Adjacent sections demonstrate both THir and choline acetyltransferase immunoreactivity in the cells in this group, as well as strong acetylcholinesterase activity but not dopamine immunoreactivity. These observations indicate that many cholinergic neurones in the posterior nucleus basalis of Meynert of the marmoset contain tyrosine hydroxylase, and suggest that both acetylcholine and catecholamine may be synthesised as co-localised neurotransmitters within the same magnocellular neurones. We observe no THir cells in similar areas of the basal forebrain of either rhesus or talapoin monkeys.

Animals

Photothrombotic lesions of the frontal cortex impair the performance of the delayed non-matching to position task by rats.

The effects of photochemically induced lesions of the frontal cortex on the short-term memory capacity of the rat have been investigated using the delayed non-matching to position task. Pretrained animals received lesions and were tested 4 days after surgery and twice per week for 3 weeks. The lesions produced a profound impairment of performance of this task which was still evident 3 weeks after surgery. Spontaneous locomotor activity was recorded 7 days after surgery and no difference was found between the control and lesion group. These effects indicated a generalized disruption of performance of this task in the absence of motor dysfunction. These results suggest that photothrombotic lesions of the frontal cortex can produce reliable, long-term behavioural deficits.

Animals

Behavioural analysis of unilateral monoamine depletion in the marmoset.

Unilateral stereotaxic injections of 6-hydroxydopamine (6-OHDA) into the nigrostriatal bundle of marmosets (Callithrix jacchus) produced substantial losses of tyrosine hydroxylase immunoreactive neurons from the substantia nigra, and mean dopamine (DA) depletions of 98-99% in the caudate nucleus, putamen and nucleus accumbens, and of 91-97% in frontal cortex, on the side of the lesion. Noradrenaline (NA) and 5-hydroxytryptamine (5-HT) levels were also affected. Behavioural tests conducted pre-operatively and at regular intervals during the 6 mths following surgery revealed persistent deficits in the lesioned marmosets as a group compared with sham-lesioned controls, although individual marmosets sometimes recovered or showed no initial deficit on some tests. The main behavioural effects of the lesion were as follows: (i) an increase in the time spent with the head positioned ipsilaterally with respect to the rest of the body; (ii) ipsilateral spontaneous and amphetamine-induced rotation, although occasional intermittent periods of contralateral rotation and head biases were also recorded; (iii) contralateral apomorphine-induced rotation; (iv) reduced spontaneous activity; (v) ipsilateral hand preference on a conveyor belt task, although hand skill (measured as percentage errors when the speed of the belt was increased) was not affected; (vi) neglect of contralateral stimuli, both at the conveyor belt where lesioned monkeys often failed to respond on trials on which apple pieces arrived from the contralateral side, and on a test of sensorimotor neglect in which adhesive labels were placed around both feet. Comparisons of biochemical measures of the lesion with behavioural scores in individual monkeys suggest that DA depletions in excess of 95% are essential for long-term behavioural deficits.

Animals

Nigral grafts in neonatal rats protect from aphagia induced by subsequent adult 6-OHDA lesions: the importance of striatal location.

Previous studies have shown that dopamine-rich nigral grafts, implanted bilaterally into the intact neonatal brain, will provide some protection from the eating disorders induced by subsequent nigrostriatal 6-OHDA lesions. This has been repeated in the present study using unilaterally transplanted nigral grafts. Following adult lesions, the control animals displayed the full syndrome of aphagia, adipsia and akinesia. By contrast, 37% of the rats in the transplanted group recommenced eating following the adult lesion. Recovery was related to the size and position of the graft: protection was associated in particular with transplants located in the posterior-ventral neostriatum. The results are discussed in terms of specific patterns of graft-host interaction that may underlie protection of the regulation of eating from the loss of forebrain dopamine systems.

Animals

Monoamine deficiency in a transgenic (Hprt-) mouse model of Lesch-Nyhan syndrome.

The integrity of forebrain monoamine systems has been assessed both biochemically and immunohistochemically in transgenic mice carrying the mutant hprt-bm2 gene, an animal model of Lesch-Nyhan syndrome. The mutant mice manifested 20-30% depletions of forebrain dopamine, and corresponding increases in dopamine turnover. By contrast, the mutant mice manifested normal tyrosine hydroxylase immunostaining of catecholamine cell bodies and terminals throughout the forebrain, and cell counts revealed no detectable loss of ventral mesencephalic dopamine neurones. Serotonin concentrations were also depleted, whereas no significant changes were found in noradrenaline or adrenaline, methylhydroxyphenylglycol (MHPG) or 5-hydroxyindoleacetic acid. The results indicate that a primary genetic deficiency in purine salvage pathways is associated with additional changes in forebrain monoamine metabolism in mouse as in man, although these changes are less pronounced in the animal model than in the human syndrome. The biochemical changes were not associated with explicit degeneration of the associated populations of neurones.

Animals

Neonatal dopamine-rich grafts and 6-OHDA lesions independently provide partial protection from the adult nigrostriatal lesion syndrome.

Previous studies have shown that neonatally dopamine-depleted rats are subsensitive to dopamine antagonists and do not respond to homeostatic imbalances as adults. This suggests that these animals maintain themselves independent of the dopamine system. If this is so, they should be insensitive to treatment with adult 6-hydroxydopamine (6-OHDA) lesions. Other experiments have shown that dopamine-rich grafts in the neonatal brain will provide some protection from the severe ingestive deficits induced by bilateral 6-OHDA lesions in adulthood. Three groups of animals received either nigra grafts into the intact neonatal brain, neonatal 6-OHDA lesions, or both neonatal 6-OHDA lesions and nigra grafts. A fourth group served as sham-operated controls. Methylamphetamine and haloperidol challenges showed that the neonatally lesioned animals regulated locomotor activity, eating and drinking independent of the dopamine system. Remarkably, however, 80% of these nevertheless showed the full syndrome of aphagia, adipsia and akinesia in response to adult lesions. The grafts into intact group showed enhanced survival in that 36% of the rats were able to maintain themselves following the adult lesion. The graft into neonatally lesioned rats restored their activational response to pharmacological challenges but did not provide any additional protection from the adult lesion. This suggests that different mechanisms underlie the protection against adult nigrostriatal lesions provided by neonatal grafts and neonatal lesions.

Animals

Hypersensitivity to alpha-methyl-p-tyrosine suggests that behavioural recovery of rats receiving neonatal 6-OHDA lesions is mediated by residual catecholamine neurones.

Previous studies have shown that rats depleted of catecholamines (CA), and in particular dopamine (DA), as neonates are sub-sensitive to DA antagonists and do not respond to homeostatic imbalances as adults. This suggests that these animals maintain themselves independent of the DA system. If this were so, they would be insensitive to the disruption of residual CA function by treatment with the CA synthesis inhibitor alpha-methyl-p-tyrosine (alpha-MT). By contrast, rats that received neonatal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) showed a marked increase in sensitivity to alpha-MT when tested as adults. This suggests that they remain dependent upon residual CA neurones for the maintenance of normal eating.

Animals

Nigrostriatal reconstruction after 6-OHDA lesions in rats: combination of dopamine-rich nigral grafts and nigrostriatal "bridge" grafts.

In an attempt to reconstruct the nigrostriatal dopamine (DA) pathway following 6-hydroxydopamine-induced degeneration in adult rats, a novel double graft procedure has been developed. Embryonic DA-rich grafts were implanted in the vicinity of the host substantia nigra by standard procedures. An intracerebral bridge was then implanted by injection of alternative tissues along a single oblique needle penetration through the frontal pole and neostriatum to the substantia nigra. Embryonic striatal tissue bridges provided a continuous column of tissue from the nigral DA graft to the host striatum. In 3 cases, tyrosine hydroxylase immunoreactive fibres grew the full length of the striatal bridge grafts and were seen to penetrate the host neostriatum. In these three animals alone, methylamphetamine-induced rotation was significantly reduced to 44% of the baseline lesion-induced turning rate. Alternative tissues or substrates (embryonic olfactory bulb, cultured astrocytes or laminin-coated microspheres) were not effective in promoting THir fibre growth from the nigral DA grafts to the host neostriatum.

Animals

Phylogenetic aspects of the neuroepithelial bodies.

Neuroepithelial bodies (NEB) are small groups of cells bound together by desmosomes and which form part of the epithelium lining the bronchopulmonary ducts. The cells have an irregular, columnar shape often with laterally placed microvilli and unspecialized cytoplasmic protrusions into the intercellular spaces. Their most distinctive cytoplasmic feature is the numerous dense cored vesicles (DCV) located towards the basal region of each cell. A variety of peptides and the monoamine serotonin are distributed within these DCV. Evidence has been shown for the occurrence of more than one type of DCV for the co-existence of various peptides and serotonin in the same DCV and for morphological and functional variations in cells forming a NEB. In some animals the apical pole is in direct contact with the lumen of the duct, whereas in others the NEB is isolated from the lumen by either ciliated epithelial or Clara-like cells. When the apical pole contacts the lumen, the surface of each cell bears microvilli and occasionally a single cilium. The NEB of eutherian mammals are sensitive to a number of experimental procedures including hypoxia, hypercapnia and vagal stimulation. Experimental lesions above and below the nodose ganglion have shown that the major part of the innervation is afferent with collateral branches off the afferent forming efferent, cholinergic endings. A small efferent input is also derived directly from the central nervous system. These studies suggest that a minor component of the efferent innervation is derived contralaterally or from intrapulmonary ganglia. Other forms of innervation identified by transmission electron microscopy in some mammals and lower vertebrates include cholinergic reciprocal synapses, adrenergic and peptidergic nerve junctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphibians

Cholinergic grafts in the neocortex or hippocampus of aged rats: reduction of delay-dependent deficits in the delayed non-matching to position task.

Aged (24 month) rats have previously been shown to manifest delay-dependent deficits in the performance of an operant delayed non-matching to position task. In the present experiment, cholinergic-rich grafts implanted into either the neocortex or the hippocampus of aged rats are shown to reinnervate the host neocortex and hippocampus, respectively, and to provide a significant amelioration of the host animals' short-term memory impairments. The results are discussed in light of the cholinergic hypothesis of geriatric memory dysfunction.

Aging

Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions.

The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6-hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior.

Animals

Effective presentation of medical images on an electronic display station.

In summary, the following should be parts of a useful system for electronic medical image display. 1. All display scales should be linearized. 2. Contrast Limited Adaptive Histogram Equalization should be applied to all slices as they arrive at display. 3. A screen or portion thereof should be dedicated to a low-sampled index of all slices, and navigation among the slices should be accomplished by reference to this index. 4. One second access to any slice or group of slices from the index should be provided.

Diagnostic Imaging

Effect of ambient light on electronically displayed medical images as measured by luminance-discrimination thresholds.

The effect of ambient light on linearization of gray scales was studied in two experiments by measuring brightness-discrimination thresholds for stimuli as a function of ambient-light level. The luminance and contrast levels of stimuli were chosen to include typical instances encountered in electronically displayed medical images. Three ambient-light levels were used: 4 and 40 lx, which span the range that we found in well-controlled radiologic reading rooms set up with electronic displays, and 148 lx, which represents the low end of the ambient-light range found in light-box reading rooms. In the first experiment, discriminability of some test stimuli was found to change as ambient light increased. The pattern of results suggests that a single linearization function would be clinically acceptable in a reading room with ambient light ranging from 4 up to, at least, 40 lx. At 148 lx, however, the just-noticeable-difference versus intensity function is different enough to require a gray-scale linearization function other than our standard one, which is based on 4-lx ambient light. We attribute these changes in stimulus discriminability to changes in the displayed image produced by ambient light, not to changes in the visual sensitivity of the observer. In the second experiment, which controlled for the display changes produced by ambient light, we found no change in stimulus discriminability as a function of ambient light.

Adaptation, Physiological