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D I Graham

Publications and source records attributed to D I Graham.

At least 235 records · Page 13Linked to original sources
PubMed1986

[Focal cerebral infarction in the rat: II. Neuropathological study and local cerebral blood flow pattern].

We have recently reported that middle cerebral artery (MCA) occlusion in the rat produces a uniform pattern of cerebral ischemia in an acute phase. This study was done to determine if this model is also useful for quantitative evaluation of infarction size in a chronic phase. [Methods] Sprague-Dawley rats were anesthetized with halothane and left MCA was occluded via transretro-orbital approach. The following studies were done. Neuropathological study was done one week after MCA occlusion. After perfusion fixation, the brain was cut into 6 coronal slices and stained sections were examined. Local cerebral blood flow patterns were observed by 14C-iodoantipyrine autoradiographic technique 1, 2, and 5 days after the occlusion. [Results] Neuropathological studies invariably showed infarct in the cortex and the lateral part of the basal ganlia. The ratio of the infarct to the total areas of both hemispheres in 6 coronal sections was 14.05 +/- 2.66% (Mean +/- SD) in MCA occluded animals (N = 14) and 0.59 +/- 0.46% in sham operated animals (N = 12). Relative to the contralateral hemisphere, marked reduction in CBF was seen in the territory of the MCA and moderate reductions were also seen in the surrounding areas. The same pattern of increased CBF as previously reported was also seen in the ipsilateral substantia nigra and globus pallidus 1, 2, and 5 days after the occlusion. These results indicate the usefulness of this chronic focal cerebral infarction model in the evaluation of infarction.

Animals↗
PubMed1985

Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology.

Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high-grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double-tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in "selectively vulnerable" areas of the forebrain.

Animals↗
PubMed1985

Effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow and histopathology after middle cerebral artery occlusion.

We used the [14C]iodoantipyrine autoradiography technique to study the effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow (lCBF) in rats that underwent middle cerebral artery (MCA) occlusion. In untreated control animals there were profound localized reductions in 1CBF 30 minutes after MCA occlusion. These were most pronounced in neocortical areas and in the caudate nucleus ipsilateral to the MCA occlusion. In animals pretreated with nimodipine (1 microgram X kg-1 X min-1 for 30 minutes before and 30 minutes after MCA occlusion), the ipsilateral decrease in 1CBF in cortical regions was significantly less than that in control animals. The drug did not appear to alter 1CBF in the ipsilateral caudate nucleus. Neuropathological quantification of the ischemic damage present 3 hours after occlusion showed that nimodipine pretreatment reduced the volume and extent of cellular damage in the periphery but not in the core of the lesion.

Acid-Base Equilibrium↗
PubMed1985

Pure cortical ischemia versus striatal ischemia. Circulatory, metabolic, and neuropathologic consequences.

Selective ischemic damage was produced either involving only the cortex or together with the striatum by occlusion of the middle cerebral artery proximal or distal to the lenticulostriate artery in the rat. The consequences in local cerebral blood flow, local cerebral glucose utilization, and neuropathology were investigated in the acute stage of ischemia. Caudate damage produced by proximal occlusion resulted in such secondary alterations as enhanced blood flow and metabolism in areas remote from the main lesion, such as in the globus pallidus and substantia nigra ipsilateral to occlusion. After distal occlusion, however, there were two patterns distinctly different from each other in the appearance of the autoradiograms. One was ipsilateral and the other was contralateral enhancement of blood flow and metabolism involving the striato-pallido-nigral axis without any striatal damage. We therefore suggest that these secondary alterations in circulation and metabolism contribute to a varied neurological dysfunction after focal cerebral ischemia. Furthermore, our currently introduced model of selective ischemic lesioning is important in studying the roles of cortical and striatal influences in ischemic pathophysiology.

Animals↗
PubMed1985

Meningo-encephalitis accompanying retinochoroiditis in a murine model of congenital toxoplasmosis.

A histopathological study of the brains of adult mice infected in utero with Toxoplasma gondii and presenting manifestations of ocular toxoplasmosis is reported. All brains contained Toxoplasma tissue cysts. A sub-acute/chronic meningo-encephalitis was the main feature of the inflammatory response in the brain. Microscopical features suggest that autoimmune processes may play a part in the disease. We suggest that our mouse model will provide a simple and inexpensive tool for the investigation of histopathological processes in the CNS resulting from congenital Toxoplasma infection.

Animals↗
PubMed1985

Ultrastructure of cerebral arteries following experimental subarachnoid haemorrhage.

Scanning and transmission electron microscopy have been used to examine the ultrastructure of cerebral arteries taken from dogs up to nine days following the injection of autologous blood into the suprachiasmatic cistern and using meticulous perfusion-fixation technique. No ultrastructural changes in the cerebral arteries were noted either at sites of radiologically demonstrated arterial constriction or elsewhere. The only abnormality noted was the presence of some leucocytes and macrophages in the subarachnoid space surrounding the arteries. These results are discussed in relation to changes in cerebrovascular reactivity that occur at this stage following subarachnoid haemorrhage.

Animals↗
PubMed1985

Selective control of human glioma cell proliferation by specific cell interaction.

Cells cultured from anaplastic astrocytoma (Kernohan and Sayre, grades III and IV) will proliferate on confluent monolayers of normal glia, while cells cultured from normal brain will not. The growth of a cell line containing a high proportion of well-differentiated glioma cells (G-CCM) was partially inhibited, though not as much as normal glia, while the growth of a cell line made up of less differentiated cells (G-UVW) was enhanced by the normal glia. Although non-glial confluent monolayers also inhibited the growth of normal glia, this was less specific, as one normal glial line (N-DUT) grew on fibroblasts and intestinal epithelium, although it was unable to do so on normal glia. It is suggested that this may be a useful method for examining reduced density limitation of growth, discriminating between normal and malignant glia, and for separating glioma cells from contaminating normal cells.

Cell Communication↗
PubMed1985

Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema.

A new model for establishing a successful and consistent arterial recirculation has been devised following middle cerebral artery (MCA) occlusion in the rat. A snare ligature was introduced at the stem of the MCA just distal to the lenticulostriate branches, and occlusion and recirculation were performed by pulling and releasing the thread. This method had an advantage over the use of a small clip which caused damage to the artery without good recirculation. Study of local cerebral blood flow using carbon-14 (14C)-iodoantipyrine, of cerebrovascular permeability using 14C-aminoisobutyric acid, and of brain-water content using the microgravimetric technique was performed upon recirculation following various periods of occlusion and compared with the results in permanent ischemia. A reactive hyperemia was noted within the previously ischemic area immediately upon recirculation following either a 30-minute or a 2-hour ischemic period. One or 2 hours later, delayed hypoperfusion developed in this region, but the circulation over the periphery of the ischemic area recovered well. Cerebrovascular permeability was not, however, altered during the time courses studied. Topographic changes in tissue specific gravity were compared between permanent and transient ischemia in the corresponding time-courses. Although there was a greater decrease in tissue specific gravity following recirculation when the ischemic period was maintained longer, edema formation was resolved by recirculation. Further study is required to determine thresholds of ischemic brain damage and edema formation at recirculation following focal cerebral ischemia.

Aminoisobutyric Acids↗
PubMed1984

Diffuse axonal injury in head injuries caused by a fall.

82 cases of diffuse axonal injury were found at necropsy in 635 patients with fatal nonmissile head injuries. 13 of these injuries were attributable to falls, and in all the patients fell from a considerable height. Diffuse axonal injury was not found in those with head injuries caused by a simple fall--ie, a fall from not more than the person's own height--but there was a statistically significant association between the presence of diffuse axonal injury and falls from a considerable height. These results indicate that diffuse axonal injury rarely, if ever, occurs as a result of a fall unless the patient has fallen some distance.

Accidents↗
PubMed1984

Effects of captopril on cerebral blood flow in normotensive and hypertensive rats.

Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Functional consequences of unilateral lesion of the locus coeruleus: a quantitative [14C]2-deoxyglucose investigation.

The functional consequences, as reflected in local rates of glucose utilization, of ablation of the locus coeruleus (the nucleus from which a major portion of the ascending noradrenergic fibres arise) have been examined in conscious rats with the quantitative autoradiographic [14C]2-deoxyglucose technique. Measurements of glucose utilization were made 72 h after histologically verified unilateral electrolytic lesions of the locus coeruleus. In the overwhelming majority of the 35 grey matter regions examined, the rate of glucose utilization was unaltered by lesions of the locus coeruleus, and in the limited number of CNS regions in which significant alterations were observed, the magnitude of the changes was invariably modest (less than 20% different from sham-operated control animals). Reductions in glucose use were observed in ipsilateral ventral (by 14%) and lateral thalamic nuclei (by 17%), and rates of glucose utilization in most regions of cerebral cortex were significantly lower (about 10%) in the ipsilateral hemisphere relative to the hemisphere contralateral to the lesion. In one region, the median raphe nucleus, glucose utilization was significantly elevated (by 19%) following lesions of the locus coeruleus. Attempts to accentuate the effects of locus coeruleus lesions by pharmacological manipulation of CNS adrenoreceptors by means of the systemic administration of phenoxybenzamine (30 mg/kg, 40 min prior to measurement of glucose use) in animals bearing unilateral locus coeruleus lesions were unsuccessful; the modest alterations in glucose utilization observed following locus coeruleus lesion alone were even less pronounced in lesioned animals receiving phenoxybenzamine. The alterations in local glucose utilization provoked by phenoxybenzamine were similar in sham-lesioned and locus coeruleus-lesioned animals. It would appear that the functional consequences, in terms of glucose utilization, are much less pronounced when a single neurotransmitter system (in the present studies, noradrenergic neurones) is lesioned than when a multiple neurotransmitter, functionally integrated pathway (such as the visual system) is disrupted.

Animals↗
PubMed1984

Focal cerebral ischemia in the rat: topography of hemodynamic and histopathological changes.

We studied local cerebral blood flow, as measured by autoradiography with digital image processing and by tissue morphology, in six rats 4 hours after occlusion of the proximal middle cerebral artery. A consistent, three-dimensional pattern of graded reductions in local cerebral blood flow involved the affected hemisphere, with a densely ischemic zone (local cerebral blood flow less than 3 ml/100 gm/min) in the dorsolateral caudate putamen and the adjacent frontoparietal cortex. In the frontoparietal cortex, the normal laminar pattern of local cerebral blood flow was disrupted, and there was a transcortical gradient in flow, with pronounced ischemia in deeper layers and relatively preserved superficial flow. Comparisons of autoradiographic findings with histopathological abnormalities in adjacent frozen sections showed that the region of ischemic damage corresponded closely with the area of greatest reduction in blood flow. Although around this region local cerebral blood flow increased centrifugally, a striking finding was that flow density changed abruptly (a tenfold variation in flow within a 1 to 2 mm interval) at the edge of the pathological lesion. Penumbral conditions may therefore exist in only a very narrow zone 4 hours after onset of focal ischemia. After occlusion of a major cerebral artery, the pattern of local cerebral blood flow changes appears to depend on interactions among vascular architecture, reductions in perfusion pressure, alterations in metabolic demands, and variations in local vascular resistance.

Animals↗
PubMed1984

Encephalitis in mice with congenital ocular toxoplasmosis.

The brains of mice with congenital ocular toxoplasmosis were examined histologically. Toxoplasma tissue cysts and a subacute/chronic meningo-encephalitis were present in the brains of all infected mice. The findings were very similar to those seen in human congenital toxoplasmosis. The murine model of congenital toxoplasmic encephalitis described in this paper will be valuable in the study of the pathogenesis, natural history and treatment of this condition.

Animals↗
PubMed1984

Toxoplasma infection and response to novelty in mice.

Three groups of mice were infected with Toxoplasma and used for behavioral testing using a Y-maze. One group was infected when adult and two groups congenitally, one of these born to dams infected during gestation, the other to dams chronically infected prior to mating. In an initial habituation period each mouse was exposed to a black arm and stem of the maze, entrance to a white arm being blocked by a transparent door. In a subsequent free-choice trial both arms were black and the mouse was free to explore all parts of the maze. During both periods infected mice were more active than controls. Infected mice engaged in less grooming behavior indicative of less approach-avoidance conflict than controls prior to entry into a choice arm at the beginning of the free-choice trial. Infected mice spent more time in the familiar than in the novel (previously blocked) arm during the free-choice trial; conversely, uninfected mice spent more time in the novel than in the familiar arm. It is suggested that the reported behavioural changes would lead to dissemination of the infection in the environment by ultimately making infected mouse intermediate hosts more susceptible to predation by domestic cats, the definitive hosts of Toxoplasma.

Animals↗
PubMed1984

Interrelationship between differentiation and malignancy-associated properties in glioma.

The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake and glutamine synthetase were used as indicators of astroglial differentiation. Plasminogen activator and tumour angiogenesis factor were the malignancy-associated markers. The normal adult brain-derived lines showed some differentiated astroglial features and expressed low levels of the malignancy-associated properties. The foetal cultures contained highly differentiated astroglia while the glioma lines showed considerable phenotypic heterogeneity from highly differentiated to undifferentiated. The least differentiated glioma cells exhibited the highest plasminogen activator activities. The density-dependent control of phenotypic expression was also investigated. High affinity GABA uptake, and GFAP in rat C6 glioma cultures, increased with increasing monolayer cell density, events probably mediated by an increase in the formation of cell-cell contacts at confluence. Plasminogen activator activity decreased with increasing cell density.

Adult↗
PubMed1984

The effect of congenital Toxoplasma infection on mouse activity and relative preference for exposed areas over a series of trials.

Previous studies showed that mice with congenital Toxoplasma infections tend to be much more active and tend to show a smaller relative preference for more exposed and novel areas than do uninfected controls. However, in those studies, mice were exposed to behavioural testing procedures once only. Results described here show that these differences (and differences defaecation) are more than just transitory phenomena observed on a first exposure to a novel area. The differences between infected and uninfected mice were clear during each of five separate trials; moreover, they tended to increase from the first to the fifth trial. The possible implications of these findings for the continuation of the life-cycle of the parasite in the environment are considered.

Analysis of Variance↗