Search PubMed⌕ Search

Biomedical subjects

U Dirnagl

Publications and source records attributed to U Dirnagl.

At least 109 records · Page 6Linked to original sources
PubMed1995

Global cerebral ischemia in the rat: online monitoring of oxygen free radical production using chemiluminescence in vivo.

Using online in vivo chemiluminescence (CL), we studied for the first time continuously the production of reactive oxygen species (ROS) after global cerebral ischemia and the relationship of ROS production to CBF. In anesthetized rats equipped with a closed cranial window, the CL enhancer, lucigenin (1 mM), was superfused onto the brain topically. CL was measured through the cranial window with a cooled photomultiplier, and CBF was measured simultaneously with laser-Doppler flowmetry. Reperfusion after 10 min (n = 8) of global cerebral ischemia led to a CL peak to 188 +/- 77% (baseline = 100%) within 10 +/- 4 min. After 2 h of reperfusion, CL had returned to 102 +/- 28%. Reperfusion after 20 min (n = 8) of ischemia increased CL to 225 +/- 48% within 12 +/- 3 min. After 2 h, CL was still increased (150 +/- 44%, p < 0.05 compared with 10 min of ischemia). CL after 10 min of ischemia was neither affected by brain topical free CuZn-superoxide dismutase (SOD) (100 U/ml, n = 3) nor by i.v. administration of free CuZn-SOD (104 U/kg, followed by 104 U/kg/h, n = 3). The CBF hyperfusion peak on reperfusion preceded the CL peak in all experiments by several minutes. In additional in vitro experiments we investigated the source of CL: Intracellular loading of lucigenin was demonstrated in cultured CNS cells, and a very similar pattern of CL as in the in vivo preparation after ischemia developed in rat brain slices after 15 min of hypoxia, which was unaffected by free CuZn-SOD (100 U/ml) but strongly attenuated by liposome-entrapped CuZn-SOD. We conclude that lucigenin-enhanced CL is a promising tool to study ROS production continuously from the in vivo brain of experimental animals and brain slices, and that the CL signal most likely derives from the intracellular production of superoxide. The production of ROS is preceded by reperfusion, is burst-like, and is dependent on the duration of the ischemic interval.

Acridines↗
PubMed1995

Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: a near-infrared spectroscopy study.

We used near-infrared spectroscopy (NIRS) to study noninvasively the influence of aging on changes in the local concentration of oxygenated hemoglobin ([HbO2]), reduced hemoglobin ([HbR]), and total hemoglobin ([HbT] = [HbR] + [HbO2]) during activation of brain function. Young subjects (n = 12; age, 28 +/- 4 years) performing calculation tasks showed an increase in [HbO2] [mean (arbitrary units) +/- SD, 2.36 +/- 1.07] and [HbT] (2.24 +/- 1.13) in the frontal cortex, while [HbR] (-0.11 +/- 0.48) decreased. Elderly subjects (n = 17; age, 52 +/- 10 years) showed a significantly lower mean increase (p < 0.05) in [HbO2] and [HbT] levels (1.21 +/- 1.38 and 0.72 +/- 1.41, respectively). Regression analysis supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2] (y = -0.241x + 20.062; r = -0.431, p < 0.05) as well as [HbT] (y = -0.346x + 22.496; r = -0.568, p < 0.05). We conclude that NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging.

Adult↗
PubMed1995

Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging.

The coupling of brain cell function to the vascular system is the basis for a number of functional neuroimaging methods relevant for human studies. These include methods as diverse as functional magnetic resonance imaging, positron emission tomography, single photon emission tomography, optimal intrinsic signals, as well as near infrared spectroscopy, a method that may have imaging capabilities in the near future. These methods map a specific localized brain activation through a vascular response, such as an increase in cerebral blood flow or a change in blood oxygenation. To understand these direct maps to obtain high resolution maps of localized functional brain activity, a precise knowledge of the specific underlying physiological mechanisms and methodological properties and restrictions is essential. In this article, these fundamental physiological and methodological aspects will be discussed. After reviewing how the techniques cited obtain maps of functional activity, we will discuss our current knowledge of the physiology of coupling with particular reference to the functional imaging techniques. Specifically, we will consider the function, the mediators, and the hemodynamic mechanisms of coupling and point out potential interference by diet, and neurological disease.

Brain↗
PubMed1994

Noninvasive assessment of cerebral hemodynamics and tissue oxygenation during activation of brain cell function in human adults using near infrared spectroscopy.

Near Infrared Spectroscopy (NIRS) was employed to noninvasively and continuously (temporal resolution 0.5 s) assess changes in cerebral hemodynamics and oxygenation during various functional states of the adult human brain. During cognitive stimulation (performing calculations) a frontal increase in local cerebral blood volume and oxygenated hemoglobin concentration was observed in most (10 of 12) subjects. During visual stimulation (observing a picture) this was demonstrated in the occipital region in all three subjects. Deoxygenated hemoglobin either decreased, remained unchanged or slightly increased during these procedures. Epileptic patients were examined during spontaneously occurring complex-partial seizures. During these seizures extremely large increases in blood volume and oxygenated hemoglobin concentration were measured. In conclusion, this feasibility study indicates that NIRS might become a useful and simple bedside tool to assess brain function.

Adult↗
PubMed1994

Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide.

We studied the role and relationship of the putative mediators of coupling of cerebral blood flow (CBF) and neuronal activation, adenosine (Ado) and nitric oxide (NO). Topical brain application over the whisker barrel cortex of anesthetized rats (n = 24) of the Ado receptor antagonist theophylline (Theo, 5 x 10(-5) M) for 30 min reduced the CBF response to deflection of the contralateral whiskers from 17.9 +/- 3.0% of baseline to 10.6 +/- 2.7% (P < 0.05). Coapplication of Theo (5 x 10(-5) M) and the NO synthase blocker N omega-nitro-L-arginine (L-NNA, 10(-3) M) for 30 min led to a further reduction in the CBF response to whisker stimulation to 7.5 +/- 1.3% (P < 0.05 compared with Theo alone). The CBF effect of sodium nitroprusside (10(-5) M) was not affected by Theo-L-NNA coapplication (122 +/- 25 vs. 140 +/- 25%, n = 5). Application of adenosine deaminase (1 U/ml, n = 5) reduced the CBF response to whisker stimulation from 18.2 +/- 0.7 to 10.7 +/- 1.9% (P < 0.05). Superfusion of L-NNA (10(-3) M, 30 min, n = 7) attenuated the CBF response to application of Ado (10(-4) M) from 39.4 +/- 10.4 to 22.9 +/- 10.5% (P < 0.05). N omega-nitro-D-arginine did not affect the CBF response to Ado (n = 5). We conclude that 1) Ado is involved in coupling of CBF to neuronal activation, 2) NO is involved in this response as well, and 3) there is an interaction between the vasodilator pathways of Ado and NO.

Adenosine↗
PubMed1994

Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study.

Confocal laser-scanning microscopy was used to visualize subsurface cerebral microvessels labeled with intravascular fluorescein in a closed cranial window model of the anesthetized rat. In noninvasive optical sections up to 250 microns beneath the brain surface, plasma perfusion and blood cell perfusion of individual capillaries were studied. Under resting conditions, in all cerebral capillaries the presence of plasma flow as demonstrated by the appearance of an intravenously injected fluorescent tracer within 20 seconds after injection. Plasma flow was verified even in capillaries that contained stationary erythrocytes or leukocytes; 91.1% of the capillaries contained flowing blood cells, 5.2% contained stationary blood cells, and no blood cells were seen in 3.6%. Mean blood cell velocity was 498.3 +/- 443.9 microns/s, and the mean blood cell supply rate was 35.75 +/- 28.01 cells per second. When capillaries were continuously observed for 1 minute, "on" and "off" periods of blood cell flow were noted. During hypercapnia (increase of PCO2 from 33.25 to 50.26 mm Hg), mean blood cell flux increased from 38.6 +/- 17.2 to 55.5 +/- 12.2 per second (P < .005, paired t test of mean values in six animals), and blood cell velocity increased from 519.5 +/- 254.8 to 828.5 +/- 460.8 microns/s (P = .074, paired t test of mean values in six animals). Homogeneity of blood cell flux increased as indicated by the coefficient of variation decreasing from 44.6% to 22.0%, and the portion of poorly perfused capillaries (blood cell flux, < 40 per second) decreased from 59.2% to 22.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.

BACKGROUND AND PURPOSE: We tested the hypothesis that cerebral hypoperfusion after experimental global cerebral ischemia is caused by plugging of the microcirculation with activated leukocytes using in vivo microscopic observation of the behavior of leukocytes in the cortical microcirculation during the transition from postischemic hyperperfusion to hypoperfusion. METHODS: Anesthetized and ventilated rats (n = 24) were equipped with a closed cranial window. Physiological variables and cortical regional cerebral blood flow (laser-Doppler flowmetry) were measured continuously. Leukocytes were labeled intravitally with rhodamine 6G and visualized in the microcirculation of the brain surface and outer layers of the cortex with confocal laser scanning microscopy from preischemia to 4 hours after reperfusion that followed 10 minutes of global cerebral ischemia (rCBF < 10% of control). RESULTS: In controls (n = 8), there were no signs of leukocyte activation over the 4-hour observation period. In ischemic rats (n = 16), during the transition from hyperperfusion to hypoperfusion there was no change in the behavior of leukocytes. Most notably, no capillary pluggers were seen. In the postischemic period only a slight increase of the number of leukocytes rolling along or sticking to the venular endothelium was seen, and very few capillaries were plugged by leukocytes. Extravasation of leukocytes into the brain tissue was observed in 8 rats beginning 2 hours after ischemia with a variable degree between animals. CONCLUSIONS: Because there was only mild activation of leukocyte-endothelium interaction within the first hours of reperfusion after 10 minutes of global forebrain ischemia, because no leukocytes plugged superficial cortical capillaries during the transition from hyperperfusion to hypoperfusion, and because the regional cerebral blood flow transition was very rapid, we speculate that leukocyte plugging is not responsible for the early cortical hypoperfusion seen after brief global ischemia in rats.

Animals↗
PubMed1993

Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults.

In healthy human adults, cerebral concentrations of oxygenated hemoglobin ([HbO2]) and deoxygenated hemoglobin ([HbR]) were assessed during brain activation using near infrared spectroscopy (NIRS). Measurements were made either in the frontal cortex (n = 10) during performance of cognitive tasks or in the occipital cortex (n = 6) during visual stimulation (flash-light exposure, picture observation). The typical findings during brain activation were an increase in [HbO2] and a decrease in [HbR]. We demonstrate that these findings are not due to alterations in skin blood flow. NIRS is a simple bedside technique for the assessment of hemodynamic alterations accompanying brain activation.

Adult↗
PubMed1993

Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats.

We tested the hypothesis that nitric oxide (NO) is a mediator in the coupling of cerebral blood flow to neuronal activation. The production of NO was blocked in anesthetized rats with the NO-synthase inhibitor N omega-nitro-L-arginine (L-NA). In controls, vibrissae stimulation for 60 s led to a fast (< or = 2 s), 17% increase in regional cerebral blood flow (rCBF) in the contralateral somatosensory cortex. Systemical (10 mg/kg) as well as topical (10(-3) M) application of L-NA reduced the response to stimulation by approximately 50%. Systemical application primarily attenuated the early component of the response, whereas topical application led to an attenuation throughout the whole 60-s stimulation interval. We conclude that NO is involved in rCBF coupling to neuronal activation.

Administration, Topical↗
PubMed1993

Applicability of laser-Doppler flowmetry for cerebral blood flow monitoring in neurological intensive care.

Laser Doppler flowmetry (LDF) is a technique for real-time assessment of cerebral blood flow (CBF) changes with potential clinical applicability. Experimental studies have validated that LDF allows accurate measurement of changes in CBF due to physiological and pathophysiological stimuli. Absolute quantitation of flow in ml/100 g min by LDF is not possible. The technique may be used in patients during open brain surgery and postoperatively for bedside CBF monitoring. Disadvantages of the technique are that the flow measurement is highly localized (about 1 mm3) and artifacts may be produced by movement, light or probe placement over large surface vessels. The fibre optic probes for LDF are small enough to be introduced into routinely used intraventricular pressure catheters. We suggest that simultaneous monitoring of CBF and intracranial pressure by such a device holds promise for improved management of patients with critical brain injury.

Blood Flow Velocity↗
PubMed1993

Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis.

We tested the hypothesis that the CBF response to extracellular acidosis is mediated by nitric oxide (NO). A closed cranial window, superfused with artificial CSF (aCSF), was implanted over the parietal cortex in anesthetized and ventilated Wistar rats. Regional cerebral blood flow (rCBF) was measured continuously with laser-Doppler flowmetry (LDF). The reaction of rCBF to hypercapnia (PaCO2 from 30.5 +/- 1.8 to 61.3 +/- 5.8 mm Hg by adding CO2 to the inspiratory gas) was 2.9 +/- 1.4%/mm Hg, and the reaction of rCBF to H+ (superfusion of acidic aCSF, pH 7.07 +/- 0.05) was 101.7 +/- 24.7%/pH unit. The regional NO synthase (NOS) activity was blocked by superfusing aCSF containing 10(-3) M N omega-nitro-L-arginine (L-NA, n = 10). After 30 min of L-NA superfusion, rCBF was reduced to 80.1 +/- 6.5% of baseline, and the rCBF responses to hypercapnia (PaCO2 from 30.9 +/- 2.9 to 58.8 +/- 7.7 mm Hg) and extracellular acidosis (aCSF pH 7.08 +/- 0.06) were reduced to 0.8 +/- 1.1%/mm Hg and 10.1 +/- 23.0%/pH unit, respectively (both p < 0.001). This effect was stereospecific since aCSF containing 10(-3) M N omega-nitro-D-arginine affected neither baseline rCBF nor the response to H+ (n = 5). The NOS blockade did not affect the vasodilatation by the NO donor sodium nitroprusside (n = 5, 114.3 +/- 25.1% before vs. 130.2 +/- 24.7% after NOS blockade). The results confirm the involvement of NO in the CBF reaction to hypercapnia and demonstrate for the first time that NOS blockade also strongly attenuates the H+ response of the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

Global forebrain ischaemia in the rat: controlled reduction of cerebral blood flow by hypobaric hypotension and two-vessel occlusion.

We developed and characterized a model of global forebrain ischaemia in rats, permitting control of CBF at any desired ischaemic level with minimum surgery and without anticoagulation. Both common carotid arteries are occluded temporarily and systemic arterial pressure is lowered by pooling venous blood by lower body negative pressure with a cheap suction device. By measuring rCBF continuously (laser-Doppler-flowmetry) and regulating systemic arterial pressure, the model was used to automatically control cortical rCBF at predetermined ischaemic levels at 50, 30, 15, and 5% of normal rCBF (n = 5). When both common carotid arteries were occluded and systemic arterial pressure was lowered to 55 mmHg with hypobaric hypotension (n = 5), cortical CBF always fell to less than 5% of normal rCBF (n = 5). Prompt recirculation was achieved after reopening of the carotid arteries and return to normobaric body pressure. Hypobaric hypotension with bilateral common carotid occlusion requires only carotid surgery and measurement of systemic arterial pressure; it produces global forebrain ischaemia without anticoagulation as a true step function type insult. If rCBF is measured continuously, the model can be used to control ischaemic CBF to predetermined values.

Animals↗
PubMed1993

Imaging of leukocyte-endothelium interaction using in vivo confocal laser scanning microscopy during the early phase of experimental pneumococcal meningitis.

Confocal laser scanning microscopy (CLSM) was used to investigate dynamic aspects of rhodamine 6G-labeled leukocytes in the pial microcirculation during the early phase of pneumococcal meningitis. Closed cranial windows were implanted into anesthetized rats without removing the dura mater. Leukocyte behavior was studied every hour after intracisternal (ic) injection. The number of adherent and extravasated leukocytes was determined during playback of videotaped images. Compared with results in controls, the number of adherent leukocytes increased significantly (P < .05) within 1 h after ic pneumococcal challenge, followed by a further increase up to 6 h after infection. In untreated infected rats, the number of extravasated leukocytes progressively increased from 3 to 6 h after infection. Leukocyte adherence to microvascular endothelium occurred in pial venules but not in arterioles. Dexamethasone pretreatment significantly (P < .05) attenuated leukocyte adherence and transendothelial passage of leukocytes.

Animals↗
PubMed1993

Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics.

We investigated the cerebral blood flow (CBF) response to somatosensory stimulation. Stimulation of neuronal activity was performed by deflection (2-3/s) of the mystacial vibrissae in rats over a period of 60 s, and regional cortical CBF was measured continuously in the contralateral somatosensory cortex with laser-Doppler flowmetry. CBF within the somatosensory cortex was studied through the parietal bone thinned to translucency (n = 7) or through a closed cranial window with the dura mater removed (n = 7). In addition, the differential effect of anesthetics (halothane-N2O, n = 5; thiobutabarbiturate, n = 5; and alpha-chloralose, n = 7) on the CBF response to stimulation was investigated. After a rapid increase after stimulation onset (maximum reached within 2-3 s), CBF remained above baseline with a slight tendency to decrease despite continued stimulation. On termination of stimulation, CBF fell to near prestimulation values within 2-3 s. The following mean CBF responses above baseline during the 60-s stimulation period were obtained: halothane-N2O anesthesia, 25.4 +/- 5.9%; thiobutabarbiturate anesthesia, 10.6 +/- 2.4%; and alpha-chloralose anesthesia, 16.9 +/- 2.3 (through the translucent bone) and 16.2 +/- 2.9% (closed cranial window, dura removed). We conclude that coupling of CBF to neuronal function has a very high temporal resolution (< 3 s) and that whisker deflection in rats provides a physiological stimulus to study coupling with laser-Doppler flowmetry.

Anesthetics↗