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Oxygenation-induced contraction of nonconfluent cultured human brain microvascular endothelial cells (HBECs, n = 30) was examined by video-enhanced contrast-differential interferential contrast microscopy. After administering a continuous gentle blow of pure oxygen gas to the surface of the medium just above the flattened HBEC, the plasma membrane exhibited tensioning and wrinkling, resulting in a strong contraction of the cell body by 14 +/- 7% (P < 0.001). When the cell stopped contracting, transient formation of a fiber network starting from certain spots (possibly adhesion plaques, though these were not visible in the majority of cases) and expanding to the whole cell was observed. The occurrence of fiber network formation was statistically significant (26 of 30 separate cells, P < 0.05). After cessation of oxygen delivery, the observed network of fibers broke up rapidly (in a period of 3.3 +/- 1.2 seconds) into small particles of <0.5 microm in diameter, which subsequently fused into the cellular structure. The HBEC completely recovered the control appearance. The sequential process was completed within 30 seconds and was reproduced in individual cells each time that oxygen gas was supplied. The authors conclude that the HBEC strongly contracts in response to a transient oxygenation stimulus, followed by rapid formation/disassembly of a network structure.

To determine the difference in cerebral hemodynamics between Moyamoya disease and atherosclerotic occlusion of the major cerebral arterial trunks, we measured local cerebral blood flow (CBF) and local CO2 reactivity (CO2R) by xenon-enhanced computed tomography (CT). A total of 11 adult patients with Moyamoya disease (mean age, 39.6 +/- 7.8 years) and eight patients with atherosclerotic occlusion of the major arterial trunks (mean age, 62.4 +/- 15.4 years) were studied. Regions of interest were frontal, temporal and occipital cortex, caudate, putamen and thalamus in each hemisphere. In patients with Moyamoya disease, local CBF values in the internal carotid artery territory (frontal and temporal cortex, caudate, putamen) were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. Local CO2R values in the caudate and putamen were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. These results suggest that the cerebral hemodynamics of Moyamoya disease differ from those of atherosclerotic occlusion of the major cerebral arterial trunks, and may be a result of the abundant collateral circulation through basal 'Moyamoya' vessels.

We evaluated the clinical features of 5 cases of tuberculous meningitis who had been admitted to our department from 1987 to 1994. Three patients were male and two were female. Their age ranged from 17 to 74 years old. All cases were examined by both CT and MRI before and during antituberculous treatment. Before the treatment, CT scan revealed abnormal findings such as nodular lesion suggesting tuberculoma, subarachnoid contrast enhancement or cerebral infarction in 2 cases, while MRI revealed abnormal findings such as inflammatory lesions with Gd-enhancement in 4 out of 5 patients. During the treatment, all abnormal findings except cerebral infarction disappeared. No abnormal findings were detected by CT. MRI and SPECT in one case who showed right hemiparesis and motor aphasia. In summary, CT scan could demonstrate abnormal findings in only a small portion of patients with tuberculous meningitis. One the other hand, MRI revealed various abnormal findings in most patients, and could reveal some lesions which could be responsible for the symptoms of patients. In a few patients, however, MRI could not show any lesion in spite of obvious focal neurological signs. MRI is considered to be useful for detecting the lesions in most patients with tuberculous meningitis, although its findings are not always specific for the disease.

The functional role of the endothelin (ET)B receptor in the cerebral microvessels was examined in seven anesthetized cats. The effects of intracarotidly injected IRL1620, a selective ETB receptor agonist, on the cerebral blood volume (CBV) in the cortex were examined by a photoelectric method. CBV reflects the cumulative dimensions of the cerebral microvessels. High doses of IRL1620 (0.1-1 nmol/kg) elicited a transient fall in CBV, followed by a marked and dose-related increase of CBV (P < 0.01). The CBV increase was significantly inhibited (P < 0.01) by simultaneous administration of 0.35 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis. The marked, but transient, depressor effect of IRL1620 was also attenuated (P < 0.01) by L-NMMA. The ETB receptor subtype and production of nitric oxide, probably in the endothelium, mediate the vasodilatory action of ET in the cerebral microvessels.

CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.

Hypodense periventricular white-matter lesions detected by CT (leukoaraiosis) and high-intensity T2 signals detected by MR imaging were correlated with measurements of local cerebral blood flow (LCBF), cerebral atrophy, and cognitive performance. Subjects studied included elderly volunteers who were neurologically normal (n = 6), patients with chronic cerebral infarctions and intact cognition (n = 2), patients with multiinfarct dementia (n = 14), and patients with Alzheimer dementia (n = 9). Leukoaraiosis correlated with periventricular high-intensity lesions detected by MR, LCBF reductions, cognitive impairments, and cerebral atrophy. Moderate to severe leukoaraiosis was associated with LCBF reductions in the cortex, basal ganglia, and frontal white matter. Periventricular MR lesions correlated with cerebral atrophy but not with cognitive impairments or reductions in LCBF. The exquisite sensitivity of MR revealed small lesions that did not correlate with LCBF reductions and cognitive impairments. Remote subcortical white-matter lesions detected by MR did not correlate with periventricular MR lesions, leukoaraiosis, LCBF, cerebral atrophy, or cognitive performance, indicating little clinical relevance. We concluded that diffuse cerebral hypoperfusion, particularly in combination with the poor collateral circulation of white matter surrounding the lateral ventricles, is responsible for leukoaraiosis.

To elucidate the role of leuko-araiosis observed on computed tomographic imaging among normal populations, 37 neurologically and cognitively normal volunteers ages 18 to 88 years were studied. Local cerebral blood flow was measured using stable xenon-enhanced computed tomography. Severity of leuko-araiosis and cerebral atrophy were graded on computed tomographic images. Leuko-araiosis was observed in 21.6% of normal volunteers, in 52.2% of patients with multi-infarct dementia (n = 23), and in 61.5% of patients with dementia of the Alzheimer type (n = 13). When multiple regression analysis was applied among normal volunteers, the degree of cerebral atrophy, advancing age, and local cerebral blood flow reductions of subcortical white matter correlated and contributed in that order of precedence to the presence and severity of leuko-araiosis. Combination of the unusual vascular anatomy of periventricular white matter together with cerebral hypoperfusion appears to be related to the occurrence of leuko-araiosis observed among neurologically and cognitively normal subjects. Further investigations should determine whether leuko-araiosis among this population is a risk factor for later cognitive impairments.

Methods are described for non-invasive, computer-assisted serial scanning throughout the human brain during eight minutes of inhalation of 27%-30% Xenon gas in order to measure local cerebral blood flow (LCBF). Optimized Xenon-enhanced computed tomography (XeCT) was achieved by 5-second scanning at one-minute intervals utilizing a state-of-the-art CT scanner and rapid delivery of Xenon gas via a face mask. Values for local brain-blood partition coefficients (L lambda) measured in vivo were utilized to calculate LCBF values. Previous methods assumed L lambda values to be normal, introducing the risk of systematic errors, because L lambda values differ throughout normal brain and may be altered by disease. Color-coded maps of L lambda and LCBF values were formatted directly onto CT images for exact correlation of function with anatomic and pathologic observations (spatial resolution: 26.5 cubic mm). Results were compared among eight normal volunteers, aged between 50 and 88 years. Mean cortical gray matter blood flow was 46.3 +/- 7.7, for subcortical gray matter was 50.3 +/- 13.2 and for white matter was 18.8 +/- 3.2. Modern CT scanners provide stability, improved signal to noise ratio and minimal radiation scatter. Combining these advantages with rapid Xenon saturation of the blood provides correlations of L lambda and LCBF with images of normal and abnormal brain in a safe, useful and non-invasive manner.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

We have shown that secondary vasodilation ('escape' phenomenon) during sympathetic nerve stimulation occurs in the intraparenchymal vessels but not remarkable in the pial vessels. To test a possible role of CO2 accumulation in the brain tissue in this phenomenon, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were investigated during hypercapnia in 9 cats by using a video camera photoelectric system. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min during hypercapnia (PaCO2 = 50 +/- 2 mm Hg). The intraparenchymal vessels as well as pial vessels remained constricted throughout the stimulation. Secondary dilation of the intraparenchymal vessels as seen at the later stage of sympathetic stimulation during normocapnia was not observed under the hypercapnic conditions. We assume that the arterial CO2 tension was so high that the constriction of inflow vessels could not result in accumulation of CO2 in the brain parenchyma. The accumulation of chemical metabolites as represented by CO2 is therefore considered to be the most probable mechanism underlying the escape phenomenon of the intraparenchymal vessels.

Results of measurements of LCBF and L lambda values utilizing optimal CT-CBF methods under resting conditions are reported among thirty-two neurologically normal volunteers aged between 20 and 88 years. Measurements were made during inhalation of 26-30% stable xenon gas for 8 min and serial scanning utilizing a state-of the-art CT scanner with both eyes closed and ears unplugged. LCBF values for cortical gray matter were lowest in occipital cortex and highest in frontal cortex. Gray matter flow values were also high in subcortical structures with highest values measured in the thalamus. For white matter, highest flow values were measured in the internal capsule. Changes in LCBF and L lambda values were analyzed with respect to advancing age. Significant age-related declines in LCBF values were observed in occipital cortex and frontal white matter. Significant age-related increases in L lambda values were measured in frontal and temporal cortex, caudate nucleus and thalamus. Possible explanations are offered for these age-related increases in L lambda values for gray matter, such as accumulation of lipofuscin in neurons and relative compacting of gray matter with advancing age. The latter increases the numbers of nerve cells sampled per volume of gray matter measured.