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Biomedical subjects

U Lindauer

Publications and source records attributed to U Lindauer.

28 records · Page 2Linked to original sources
PubMed1996

Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats: a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study.

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200-400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3 warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N'-nitro-L-arginine had no significant effect on the perfusion response or the tissue PO2 during CSD. During most CSD episodes, a brief decrease in MABP by 4-8 mm Hg was noted that might be caused by functional decortication during CSD.

Animals↗
PubMed1996

Role of nitric oxide synthase inhibition in leukocyte-endothelium interaction in the rat pial microvasculature.

We investigated the role of nitric oxide (NO) in leukocyte-endothelium interaction, blood-brain barrier (BBB) function and oxygen free-radical production in the rat pial microcirculation. In a closed cranial window preparation (dura removed) over the parietal cortex of pentobarbital-anesthetized Wistar rats, NO synthase (NOS) was inhibited by systemic and/or topical application of N omega-nitro-L-arginine (L-NNA) under physiological conditions and during leukotriene B4 (LTB4) activation. Circulating leukocytes were labeled by intravenous injection of rhodamine 6G. We used a confocal laser scanning microscope (CLSM) and studied leukocyte rolling and sticking in pial veins and arteries before and after NOS inhibition. At the end of the experiments, sodium-fluorescein was injected intravenously to test BBB integrity. Brain cortex oxygen free-radical production was investigated in the cranial window preparation using lucigenin-enhanced chemiluminescence (CL). L-NNA application did not lead to significant changes in leukocyte-endothelium interaction, BBB function, and oxygen free-radical production under physiological conditions [leukocyte-endothelium interaction: control (n = 5), L-NNA systemically (n = 5), L-NNA topically (n = 5): at baseline rollers/100 microns: 0.76 +/- 0.55, 0.64 +/- 0.94, 0.44 +/- 0.55 and stickers/100 microns: 0.90 +/- 0.28, 0.76 +/- 0.24, 0.84 +/- 0.42; at 60 min rollers/100 microns: 1.49 +/- 0.66, 1.21 +/- 0.99, 0.67 +/- 0.66 and stickers/100 microns: 1.04 +/- 0.20, 1.19 +/- 0.23, 1.21 +/- 0.54; oxygen free-radical production (n = 4): CL count before L-NNA application 35 +/- 17 cps, after 1 h of topical superfusion of L-NNA 38 +/- 14 cps; p < 0.05]. In contrast to the results achieved under physiological conditions, a significant further increase of rolling leukocytes and BBB permeability occurred due to NOS inhibition under LTB4-activated conditions [76 +/- 47% significant (p < or = 0.01, n = 7) further increase of rollers/100 microns due to 60 min L-NNA application following the activation period of 120 min LTB4 superfusion]. Our results support a modulatory role for NO in leukocyte-endothelium interaction and BBB permeability in the pial microcirculation when this interaction is increased.

Animals↗
PubMed1995

Nitric oxide modulates the CBF response to increased extracellular potassium.

The response of the regional cerebral blood flow (rCBF) to brain topical superfusion of 20 mM K+ was characterized in a closed cranial window preparation in barbiturate anesthetized and ventilated rats: Increasing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF elevation (measured by laser-Doppler flowmetry) of +85 +/- 37% above baseline (n = 19). This elevation was stable for > 3 h with continuous superfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ concentration. Nitric oxide synthase (NOS) inhibition by brain topical superfusion with N omega-nitro-L-arginine (L-NA) revealed (a) Addition of L-NA to high-potassium ACSF reduced the rCBF increase from +94 +/- 36% to +21 +/- 18% (p < or = 0.01, n = 7). (b) When L-NA was superfused for 60 min before increasing K+, rCBF decreased to -17 +/- 7% below baseline. Subsequent coapplication of L-NA and increased K+ induced only an elevation of +7 +/- 4% above baseline (n = 4). (c) When the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was added during NOS inhibition to restore basal tissue NO levels, the resultant level of rCBF was +28 +/- 54% above baseline. Subsequent increase of K+ in the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 89% above baseline (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
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↗
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

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

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↗