Biomedical subjects

U Dirnagl

Publications and source records attributed to U Dirnagl.

121 records · Page 7Linked to original sources

PubMed1992

Effect of catalase on regional cerebral blood flow and brain edema during the early phase of experimental pneumococcal meningitis.

Previous studies have demonstrated that the radical scavenger superoxide dismutase completely blocked the increase of regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain water content during the early phase of experimental pneumococcal meningitis in the rat. To obtain information on the nature of the reactive oxygen species involved, the effect of catalase, a hydrogen peroxide scavenger, was tested. Rats injected intracisternally with live pneumococci were either untreated or received intravenous catalase. The increase of rCBF and brain water content in infected untreated rats was significantly attenuated by catalase 6 h after intracisternal challenge. ICP increased in both infected groups, with a trend toward lower ICP with catalase treatment. Cerebrospinal fluid white blood cell counts were not significantly different between infected groups. These results and previous experiments using superoxide dismutase suggest that the increase of rCBF, ICP, and brain water content is mainly caused by superoxide or superoxide reaction products.

Animals↗

PubMed1992

In-vivo confocal scanning laser microscopy of the cerebral microcirculation.

Confocal scanning laser microscopy (CSLM) was used to study the microcirculation of the brain neocortex in anaesthetized rats. After removal of the dura mater, implantation of a closed cranial window, and intravenous injection of fluorescein, three-dimensional reconstructions of cortical capillaries were performed down to a depth of 250 microns below the pial surface. Using a one-dimensional approach (single line scanning), erythrocyte (negative contrast in fluorescently labelled plasma) and leucocyte (labelled with rhodamine 6 G) velocity and supply rate in cortical capillaries were measured. The effect of CO2-inhalation on capillary blood flow dynamics was studied. Capillaries were imaged continuously for up to 1 h without changes in flow or fluorescence pattern. However, by increasing the laser power 10-100-fold, aggregate formation was induced and capillaries were occluded, possibly due to damage to vascular endothelium. We conclude that CSLM can be used to study morphological and dynamic aspects of fluorescently labelled subsurface structures in organs of experimental animals.

Angiography↗

PubMed1992

Cerebrovascular complications of bacterial meningitis in adults.

We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bacterial meningitis. Cerebral angiography was performed in 27 patients (31.4%) who had focal deficits either clinically, on cranial CT, or both, and in patients who had persistent coma without explained cause despite 3 days of antibiotic therapy. Alterations of the vessel systems, including involvement of major arteries at the base of the brain, medium-sized arteries, small vessels, and major sinuses and cortical veins, were present in 13 of the 27 patients who had angiography. Typical cerebrovascular complications were arterial narrowing of the supraclinoid portion of the internal carotid artery; vessel wall irregularities, focal dilatations, and occlusions of distal branches of the middle cerebral artery; focal abnormal parenchymal blush; and thrombosis of the sagittal superior sinus and cortical veins. Prognosis for those patients with cerebrovascular complications was unfavorable. Six patients died, one remained in a vegetative state, four were moderately or slightly disabled, and only two recovered completely. The study showed that angiographically documented cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease.

Adult↗

PubMed1991

Imaging of leukocytes within the rat brain cortex in vivo.

Confocal laser scanning microscopy was used in a rat closed cranial window preparation in order to study rhodamin 6G-labeled leukocytes within the brain cortex in vivo. Leukocytes were visualized up to 150 microns beneath the rat brain surface in noninvasive optical sections. In pial venules, leukocytes were seen flowing with the blood stream, rolling along or sticking to the endothelium, and migrating through the vessel wall. Within cerebral capillaries, leukocyte flux, velocities, and leukocyte plugging were measured. After additional intravenous administration of fluorescein, the plasma, leukocytes, and erythrocytes were visualized simultaneously. Based on stacks of optical sections of fluorescein-labeled capillaries, the individual capillaries were localized within the three-dimensional microvascular network. The usefulness of this technique was illustrated in a feasibility study in which leukocyte sticking to the vascular walls of venules, leukocyte extravasation, and intracapillary leukocyte plugging were monitored in a model of global cerebral ischemia.

Animals↗

PubMed1991

Three-dimensional reconstruction of the rat brain cortical microcirculation in vivo.

We used confocal laser scanning microscopy (CLSM) to investigate the morphology and three-dimensional relationships of the microcirculation of the superficial layers of the rat brain cortex in vivo. In anesthetized rats equipped with a closed cranial window (dura mater removed), after i.v. injection of 3 mg/100 g of body weight of fluorescein in 0.5 ml of saline, serial optical sections of the brain cortex intraparenchymal microcirculation were taken. Excitation was at a wavelength of 488 nm (argon laser), and emission was collected above 515 nm. CLSM provided images of brain vessels with sufficient signal-to-noise ratio for three-dimensional reconstructions down to a depth of 250 microns beneath the surface of the brain. Compared to conventional fluorescence microscopy, CLSM has a much higher axial resolution and higher depth of penetration. Laser light-induced intravascular aggregates, irregularities of erythrocyte flow, or microvascular occlusions ("light and dye injury") were not apparent in the current experimental paradigm. CLSM is a promising new tool for in vivo visualization of the cerebral microcirculation. Future studies have to characterize the potential damage to the tissue dye mechanisms.

Animals↗

PubMed1990

Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat.

The effect of treatment with the potent, non-competitive NMDA receptor-channel antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) on ischemia-induced brain damage was studied in a well-characterized model of focal neocortical infarction in spontaneously hypertensive rats. Anesthesia exposure was minimized to the surgical procedure and the infarcts were allowed to mature over a 24-h period. Pretreatment with 5 mg/kg i.p. MK-801 (n = 11 control, n = 12 treated animals) 30 min before induction of focal cerebral ischemia had no statistically significant influence on infarct volumes. However, pre- and post-treatment with MK-801 5 mg/kg i.p. 30 min before induction of ischemia and 2.5 mg/kg each at 8 and 16 h after onset of ischemia, reduced infarct volumes in two separate studies by 29% (investigator J.T., n = 5 control and n = 7 treated animals) and 20% (investigator U.D., n = 8 control and n = 8 treated animals), respectively. The combined reduction in infarct volume in MK-801-treated animals for both investigators was 23% (P = 0.016, ANOVA). The findings indicate a smaller neuroprotective effect of MK-801 in spontaneously hypertensive rats subjected to focal ischemia than in previous reports using normotensive animals.

Animals↗

PubMed1990

Superoxide dismutase inhibits brain oedema formation in experimental pneumococcal meningitis.

The purpose of this study was to identify mediators of brain oedema formation in experimental pneumococcal meningitis. In a rat model of pneumococcal meningitis brain water content was significantly elevated 6 hours post infection (79.69% +/- 0.24 compared to 78.94% +/- 0.16 in the control group, mean +/- SEM, p less than 0.05). Brain oedema formation was completely blocked by superoxide dismutase (132,000 U/kg i.v. per 6 hours: n = 6), pretreatment with dexamethasone (3 mg/kg i.p., n = 3), or administration of dexamethasone at two hours after pneumococcal injection (n = 5). Pretreatment with indomethacin (10 mg/kg i.v., n = 5) attenuated the brain oedema formation. These findings suggest that oxygen derived free radicals act as mediators of brain oedema formation during the early phase of experimental bacterial meningitis. Cyclooxygenase metabolites may provide one possible source for the generation of oxygen derived free radicals in bacterial meningitis.

Animals↗

PubMed1990

Microvascular changes during the early phase of experimental bacterial meningitis.

We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 microliters of 10(7) colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 +/- 33.8% (mean +/- SD) in the untreated animals at 1 h p.i. and reached 211.1 +/- 40.5% at 6 h p.i. (p less than 0.05 compared with controls). ICP increased from 2.9 +/- 1.4 to 10.4 +/- 4.7 mm Hg at 6 h p.i. (p less than 0.05 compared with controls). Brain water content was significantly elevated (79.69 +/- 0.24 compared with 78.94 +/- 0.16% in the control group, p less than 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.v., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Autoregulation of cerebral blood flow in experimental focal brain ischemia.

The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.

Animals↗

PubMed1990

Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia.

We used laser-Doppler flowmetry to study the effect of nimodipine administered after the onset of focal cortical ischemia on regional cerebral blood flow in 16 halothane-anesthetized, mechanically ventilated Wistar rats. We selected the Wistar rats strain since it would provide a wide range of ischemia severities to test the vascular response to nimodipine. Laser-Doppler probes continuously recorded regional cerebral blood flow at two or three sites over the parietal cortex (dura intact) while brain temperature was regulated at 37 degrees C. Occlusion of the right middle cerebral and common carotid arteries reduced cerebral blood flow to a mean of 38% (range 13-77%) of baseline. Thirty minutes later, either 2 micrograms/kg/min nimodipine (n = 8) or its vehicle, polyethylene glycol 400 (n = 8), was administered by a continuous intravenous infusion. Over 60 minutes of treatment, both the nimodipine-treated and vehicle-treated groups showed a trivial (3%) mean increase in cerebral blood flow. Nimodipine failed to augment cerebral blood flow regardless of whether the cortex was severely, moderately, or mildly ischemic.

Animals↗

PubMed1989

Confocal laser microscopy to study microcirculation on the rat brain surface in vivo.

We demonstrate the feasibility of using confocal laser microscopy (CLM) to study the microcirculation on the rat brain surface. Using a closed cranial window model in vivo, microvessels in the size range of capillaries (8 microns) and dynamic events were observed through an intact dura. This study is the first step in the development of a system which simultaneously monitors vascular and metabolic processes using CLM.

Animals↗

PubMed1989

Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model.

Laser-Doppler flowmetry (LDF), a new method allowing instantaneous, continuous, and noninvasive measurements of microcirculatory blood flow in a small tissue sample, was evaluated for its accuracy in monitoring regional cerebral blood flow (rCBF) in the cortical microcirculation after focal cerebral ischemia. Wistar and spontaneously hypertensive rats (SHR, n = 19) were subjected to permanent occlusion of the middle cerebral and common carotid arteries. Absolute rCBF in a tissue sample of the ischemic hemisphere was measured autoradiographically with [14C]iodoantipyrine as a tracer and compared to rCBF measured by LDF. Additionally, the percent change in rCBF between baseline and ischemic values was compared for both methods. Absolute rCBF values recorded with LDF correlated poorly (r = 0.54) with [14C]iodoantipyrine measurements. In contrast LDF readings expressed as a percentage of ischemic vs. preocclusion readings (relative LDF readings) correlated very well (r = 0.91) with the percent change in [14C]iodoantipyrine measurements. We conclude that LDF does not provide accurate measurements of absolute rCBF values but this method allows accurate measurements of changes in rCBF due to induction of focal cerebral ischemia.

Animals↗

PubMed1989

B-waves in healthy persons.

The objective of this study was to determine, whether 0.5-2/min oscillations in intracranial pressure ('B-waves') are a physiological phenomenon. In a group of 5 patients 0.5-2/min oscillations of ventricular pressure simultaneous with oscillations in the middle cerebral artery (MCA) flow velocity, as assessed by transcranial Doppler sonography, were observed. Similar oscillations in MCA blood flow velocity were demonstrated in 8 out of 10 healthy subjects with an amplitude of about 10% of the mean flow velocity. We speculate that oscillations both in ventricular pressure and middle cerebral artery blood flow velocity are caused by rhythmic diameter changes of cerebral vessels with concomitant cerebral blood volume oscillations. Our data support the suggestion that B-waves may be physiological.

Adult↗