Magnetic resonance imaging and smooth periventricular high-signal areas.
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Aged↗
Biomedical subjects
D I Graham
Publications and source records attributed to D I Graham.
Congenital neuro-ophthalmic toxoplasmosis in the mouse.
Clinical examination of the eyes of mice with congenital toxoplasmosis provided a good indication of the extent of underlying histopathological damage in the eye, but was of little value for predicting neuropathological severity. Furthermore, the dye-test titre was not related either to the degree of ocular damage or to the severity of brain damage.
Animals↗
Quantitative assessment of early brain damage in a rat model of focal cerebral ischaemia.
A method for the volumetric assessment of early cerebral infarction, together with its statistical and biological validation, is described. In halothane anaesthetised rats the stem of the right middle cerebral artery was occluded and 3 hours later (with full monitoring of respiratory and cardiovascular status) the animals were killed by perfusion fixation. In normotensive normocapnic animals the volume of infarction was 52 +/- 4 mm3 in the cerebral cortex and 21 +/- 1 mm3 in the corpus striatum. The reproducibility of the volumetric assessment was found to be excellent (coefficient of correlation 0.995 on 18 replicate measurements). The minimum number of stereotactic levels which must be assessed to yield accurate volumetric measurements of infarction is 8. The method is sensitive at detecting alterations in the amount of infarction. For example, it can readily detect the increase in amount of structural damage in cerebral cortex following a transient episode of hypotension. This approach allows an objective assessment of drug therapy and management strategies in the treatment of cerebral infarction.
Animals↗
Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry.
Experimental intracerebral hemorrhage has been shown to cause extensive cerebral ischemia. This study was performed to ascertain the time course of these changes and also to examine the type of brain damage that may occur under such circumstances. Halothane anesthesia was induced in rats, and 25 microliter autologous blood was injected into the caudate nucleus; the effects were studied with autoradiographic measurement of local cerebral blood flow and capillary permeability, and also by light microscopy and histochemical techniques. Blood flow returned to normal or to slightly increased levels within the first 3 hours, and ischemic levels of flow were found to persist only to a marginal degree beyond 10 minutes after the lesions were made. Capillary permeability was maximum during the first 30 minutes after the hemorrhage and diminished with time. Structural evidence of ischemic damage was localized to the cortex overlying the hemorrhage, but was not seen in the caudate nucleus. Nevertheless, histochemical investigation did reveal an area of disturbed enzyme function in the striatum. This finding of biochemical disturbance without structural evidence of ischemic damage reveals that there is an area around the hematoma that, although demonstrating disturbed function, does not show structural damage, and the milieu of this partially injured brain may be implicated in the delayed development of the ischemic brain damage that follows intracerebral hemorrhage in man.
Animals↗
Experimental intracerebral hemorrhage: effects of a temporary mass lesion.
Late pathophysiological events after the production and subsequent removal of an intracerebral mass were investigated using a mechanical microballoon model to simulate intracerebral hemorrhage. Immediately following balloon inflation in the caudate nucleus of rats, there was a significant increase in intracranial pressure to 14 +/- 1 mm Hg (mean +/- standard error of the mean), accompanied by a reduction in cerebral blood flow (CBF) in the ipsilateral frontal cortex, as measured by the hydrogen-clearance technique. Carbon-14-iodoantipyrine autoradiography revealed a significant reduction in the CBF of the ipsilateral caudate nucleus 4 hours after balloon inflation: 31% of the caudate nucleus had a CBF of less than 20 ml X 100 gm-1 X min-1 compared to only 1% in the sham-treated control group (balloon insertion without inflation). The rats with an intracerebral mass exhibited a significant increase in the volume of ischemic damage in the ipsilateral caudate nucleus (17.1% of total volume) compared to only 1.7% in the sham-treated group; however, there was no evidence of cerebral edema. Ischemic damage and reduced CBF persisted for 4 hours after transient inflation of a microballoon in the caudate nucleus. This suggests that ischemic damage occurs at the time of formation of the lesion and is not prevented by its early removal.
Animals↗
The hemodynamic effects of internal carotid artery stenosis and occlusion.
The purpose of this study was to determine in subhuman primates whether hemodynamic mechanisms (as compared with embolic mechanisms) contribute to cerebral ischemia following carotid artery occlusion or stenosis. Following carotid artery occlusion there was loss of cerebral autoregulation: cerebral blood flow (CBF) measured with the xenon-133 technique became passively dependent upon the mean arterial blood pressure (MABP) over an MABP range of 30 to 110 mm Hg. By contrast, autoregulation was preserved in normal animals and in animals with a 90% carotid artery stenosis. Regional CBF was measured with carbon-14-labeled iodoantipyrine autoradiography in normotensive baboons, in hypotensive animals, and in hypotensive animals with carotid artery occlusion or stenosis. With carotid artery occlusion and hypotension, reduced levels of local CBF were seen ipsilaterally in the boundary zones between the anterior and middle cerebral arteries with 35% of the area of an anterior section through the hemisphere displaying a CBF value of less than 20 ml/100 gm/min. Comparable values with hypotension were 21% with carotid artery stenosis, 20% with no proximal vascular lesion, and 1% in normotensive animals. These areas of reduced CBF corresponded with areas of boundary-zone ischemia seen with light microscopy. The study suggests that while hemodynamic ischemia develops with carotid artery occlusion, it does not occur with even a 90% carotid artery stenosis or in normal animals.
Animals↗
Experimental intracerebral mass: time-related effects on local cerebral blood flow.
Cerebral blood flow (CBF) was measured at different times during the first 150 minutes following an experimental space-occupying lesion produced with a 50-microliter microballoon in rats. Local CBF was measured with the carbon-14-labeled iodoantipyrine quantitative autoradiographic technique. A region of local ischemia developed around the mass, while the remote effects of the mass were minimal. The focal ischemic lesion enlarged with time, and simulated removal of the lesion within this design did not alleviate the ischemia.
Animals↗
An immunohistochemical study of glial and neuronal markers in primary neoplasms of the central nervous system.
Paraffin-embedded tissues from 56 primary neoplasms of the central nervous system and seven cases of non-neoplastic reactive astrocytosis were examined by immunoperoxidase techniques on serial sections using monoclonal antibodies to glial fibrillary acidic protein (GFAP) and the 68 kDa neurofilament subunit and monospecific polyclonal antibodies to alpha- and gamma-enolase. gamma-Enolase was present in all neoplasms of neuronal origin, but was also present in anaplastic gliomas (particularly in giant cells), in some well-differentiated astrocytomas and reactive astrocytes. The cells containing gamma-enolase in these cases appeared morphologically identical to those containing alpha-enolase and GFAP in adjacent serial sections. No relationship was found between gamma-enolase immunoreactivity and cellular anaplasia in the gliomas studied. Subependymal neoplasms from patients with tuberose sclerosis exhibited evidence of both astrocytic and neuronal differentiation, sometimes in morphologically distinct cell populations, consistent with their suggested origin from a primitive cell line.
Astrocytes↗
The immunocytochemical demonstration of Toxoplasma antigen in the brains of congenitally infected mice.
The peroxidase anti-peroxidase immunocytochemical staining method was used to identify Toxoplasma antigen in paraffin embedded sections of the brains of 22 mice congenitally infected with the parasite. Intact Toxoplasma tissue cysts were readily demonstrated in the brain in all cases. In 4 of the 22 infected mice there was evidence of rupture of the cyst wall and/or presence of extra-cystic Toxoplasma antigen. Further support for the extra-cystic location of Toxoplasma antigen was obtained by electron microscopy of reprocessed tissue which revealed endozoites in the area immediately surrounding a ruptured cyst. The possible implications of these findings in relation to the pathogenesis of congenital toxoplasmic meningo-encephalitis are discussed.
Animals↗
Nimodipine and the haemodynamic and histopathological consequences of middle cerebral artery occlusion in the rat.
The effect of the administration of nimodipine (1 microgram kg-1 min-1), initiated 5 min after occlusion of a middle cerebral artery (MCA), upon cerebral haemodynamics ([14C]iodoantipyrine autoradiography) and neuropathological outcome (volume of histologically ischaemic tissue) was investigated in anaesthetized rats. Measurements were made of the level of local CBF (LCBF) in a total of 37 neuroanatomically defined areas, either ipsilateral or contralateral to the occluded vessel, and the autoradiograms were examined using a new approach to quantitative densitometry that employed a frequency distribution analysis of the CBF in sections of the brain at different coronal planes. Both methods of analysis showed that nimodipine, administered after the ischemic event, did not modify the pattern of CBF distribution after MCA occlusion. The extent of ischaemic brain damage was determined by histological examination. There was no evidence that the extent of ischaemic damage, either in sections at eight different coronal planes or in overall volume, was significantly different in animals that received nimodipine from that observed in animals that received only the vehicle used to dissolve the drug. The lack of cerebral circulatory and neuropathological alterations when nimodipine administration is initiated after occlusion of the MCA is contrasted with the higher levels of LCBF and the reductions in the volume of ischaemic tissue that were found when nimodipine was administered before occlusion of the artery.
Animals↗
Comparison of quantitative autoradiographic and xenon-133 clearance methods: correlation of gray and white matter cerebral blood flow with compartmental blood flow indices.
The relationships between CBF in gray and white matter to those of the fast and slow components of xenon-133 clearance curves remain uncertain. CBF was measured in 13 anaesthetized baboons under a variety of conditions, using both the xenon-133 clearance technique and [14C]iodoantipyrine quantitative autoradiography. There was a linear relationship between CBF, as determined by the stochastic (height/area) analysis of the clearance curve, and mean CBF determined from the autoradiograms (r = 0.94, p less than 0.001, slope = 0.86 +/- 0.09). There was also a linear correlation between the fast-flow component (measured with xenon-133) and blood flow in the cerebral gray matter (measured with [14C]iodoantipyrine) (r = 0.92, p less than 0.001, slope = 0.69 +/- 0.15) and between the slow-flow component (with xenon-133) and blood flow in white matter (with [14C]iodoantipyrine) (r = 0.79, p less than 0.01, slope = 0.81 +/- 0.10). In the primate brain, the fast- and slow-flow indices therefore appear to be representative of CBF in gray matter and white matter, respectively, whereas the stochastic analysis provides a stable measure of mean CBF within the tissue monitored.
Animals↗
Active management of the unconscious eclamptic patient.
Of the many complications which may develop after eclamptic seizures, prolonged unconsciousness is one of the most difficult for obstetricians to manage as the pathophysiology of this condition remains largely unknown. Computed axial tomography (CT scan) was performed on 20 unconscious eclamptic patients, and autopsy was obtained on an additional two patients. Changes compatible with cerebral oedema were demonstrated in 75% of patients; cerebral haemorrhage occurred in 9%. A programme of intensive neurological management aimed at optimizing cerebral perfusion and controlling intracranial pressure is outlined. We have reduced the mortality rate for unconscious eclamptic patients from 50% to 17% in our institution.
Adolescent↗
D-1 dopaminergic and beta-adrenergic stimulation of adenylate cyclase in a clone derived from the human astrocytoma cell line G-CCM.
Clones have been isolated from the human astrocytoma cell line G-CCM. Homogenates of clone D384 contain an adenylate cyclase that is stimulated by 3,4-dihydroxyphenylethylamine (dopamine), noradrenaline, and isoprenaline with Ka apparent values of 4, 56, and 2.7 microM, respectively. The Ka apparent value for dopamine was increased by the D-1 antagonist cis-flupenthixol, 25 and 100 nM, to 23 and 190 microM, respectively, but was unaffected by propranolol (1 microM). Noradrenaline stimulation of adenylate cyclase was only partially inhibited by either propranolol (10 microM) or cis-flupenthixol (1 microM). Propranolol (10 microM), but not cis-flupenthixol (1 microM), prevented stimulation by isoprenaline. The stimulation of adenylate cyclase by dopamine and noradrenaline remained unchanged in the presence of phentolamine (1 microM) and sulpiride (1 microM). These results suggest that clone D384 contains both D-1 dopaminergic and beta-adrenergic receptors coupled to adenylate cyclase. Dopamine stimulates D384 adenylate cyclase through D-1 receptors, isoprenaline via beta-receptors, and noradrenaline through both receptors.
Adenylyl Cyclases↗
Analysis of abnormalities in pituitary gland in non-missile head injury: study of 100 consecutive cases.
Pituitary glands, obtained at necropsy from a consecutive series of 100 patients who had died as a result of non-missile head injuries, were examined to define the incidence and pathogenesis of abnormality.
Adolescent↗
Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.
Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury.
Adolescent↗
Early hemodynamic changes in experimental intracerebral hemorrhage.
A model of experimental intracerebral hemorrhage is described in which carefully controlled volumes of autologous blood were injected at arterial pressure into the caudate nucleus of the rat. A comparison of intracranial pressure changes and local cerebral blood flow (CBF) was made between three groups of rats, each receiving different injection volumes, and sham-operated control rats by monitoring intraventricular pressure and by obtaining quantitative autoradiographic measurements of CBF within 1 minute of the experimental hemorrhage. Cerebral blood flow was reduced both around the hematoma and in the surrounding brain. This change was strongly volume-dependent and was not accompanied by significant alterations in cerebral perfusion pressure. This finding suggests that the degree of ischemia at the time of an intracerebral bleed depends on the size of the lesion, and implicates local squeezing of the microcirculation by the hematoma, rather than a generalized alteration in perfusion pressure, as the cause of ischemia.
Animals↗
Cardiovascular and cerebrovascular effects of isoflurane-induced hypotension in the baboon.
Mean arterial pressure (MAP) decreased by 10, 20, 40, and 50% of its baseline value in six anesthetized baboons with the administration of increasing concentrations of isoflurane. Mean arterial pressure, right atrial pressure, pulmonary artery pressures, and cardiac output were measured at each decrement in arterial pressure, and after the withdrawal of the isoflurane. At the same times, cerebral blood flow, the cerebral metabolic rate for oxygen, and the cerebral metabolic rate for glucose were determined. Cerebrovascular reactivity was assessed before, during, and after the administration of isoflurane, and morphologic evidence of ischemic cell change was sought at the end of the investigation. Isoflurane produced dose-related decreases in systemic vascular resistance and MAP; heart rate, cardiac output, and stroke volume did not change significantly. Although cerebral metabolism was depressed in a dose-related manner, the response of the cerebral blood flow (CBF) was biphasic. At low isoflurane concentrations, CBF decreased significantly and then increased to reach baseline values at the highest concentration. Cerebrovascular reactivity was intact at baseline and at the 20% decrement in MAP; it was impaired at the 50% decrease in MAP and when studied 100 min after the withdrawal of isoflurane. There was no morphologic evidence of ischemic cell damage in any animal.
Animals↗
Gliding contusions in nonmissile head injury in humans.
"Gliding" contusions, ie, hemorrhagic lesions in the parasagittal white matter, were analyzed in 434 fatal nonmissile head injuries in humans. It is concluded that gliding contusions are a type of diffuse brain damage occurring at the moment of injury. Gliding contusions are significantly associated with road-traffic accidents, with the absence of a skull fracture or a "lucid interval," and with the presence of diffuse axonal injury and deep hemispheric traumatic hematomas.
Accidents, Traffic↗