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I Kanno

Publications and source records attributed to I Kanno.

At least 19 recordsLinked to original sources

Cyclooxygenase-pathway participates in the regulation of regional cerebral blood flow in response to neuronal activation under normo- and hypercapnia.

The present study was designed to investigate whether cyclooxygenase products are involved in the regulation of the regional cerebral blood flow, evoked by somatosensory activation (evoked rCBF) under normo- and hypercapnia. Indomethacin (IMC) was used as cyclooxygenase inhibitor. It was applied intravenously (i.v., 10 mg/kg/h) in two experimental protocols-before hypercapnia (i) and after hypercapnia (ii). Somatosensory activation was induced by electrical hind paw stimulation (5 Hz frequency, 5 s duration, 1.5 mA). The evoked rCBF-response was measured in alpha -chloralose anesthetized rats using laser-Doppler flowmetry. IMC abolished completely the effect of hypercapnia on the baseline level of CBF. The drug reduced significantly evoked rCBF-response also. The inhibitory effect of IMC on evoked rCBF-response is better expressed under normocapnia (approximately 70%) than that under hypercapnia (approximately 40%). After IMC application, the normalized evoked rCBF curves peaked earlier as compared to that before its application (P<0.05), although the rise time of 0.5 s was nearly constant regardless of stimulus frequency. In conclusion, the results suggest a participation of IMC-sensitive and cyclooxygenase-dependent mechanisms in the regulation of evoked rCBF, induced by somatosensory stimulation.

Acid-Base Equilibrium↗

Hyperoxia modified activation-induced blood oxygenation level-dependent response of human visual cortex (V1): an event-related functional magnetic resonance imaging study.

To investigate the effect that hyperoxia has on the blood oxygenation level-dependent (BOLD) response to visual stimulation of human V1, an event-related functional magnetic resonance imaging technique was applied. The event-related paradigm consisted of 2 s of stimulation by a checkerboard reversing at a frequency of 8 Hz, followed by 18 s of control scans. The peak height and peak time of the BOLD response curves were compared under normoxic and hyperoxic conditions. It was found that the peak height was larger and the peak time shorter for hyperoxia than for normoxia. These results suggest that hyperoxia modified the activation-induced hemodynamic response of human V1.

Adult↗

Temporal characteristics of event-related BOLD response and visual-evoked potentials from checkerboard stimulation of human V1: a comparison between different control features.

This work is concerned with the temporal characteristics of event-related blood oxygenation level-dependent (ER-BOLD) and visual-evoked potential (VEP) signals produced by checkerboard stimulation of human V1. The study investigated whether different control features produce different amplitude VEPs, and if so, whether this corresponds to different ER-BOLD responses. The results showed that there was a difference in the amplitude of the P1-N1 components of the VEPs, and also in the magnitude and extent of the ER-BOLD responses. These results suggest the possibility that the P1-N1 components may be related to the difference in the magnitude and extent of the ER-BOLD response. Magn Reson Med 45:212-216, 2001.

Adult↗

Bayesian technique for investigating linearity in event-related BOLD fMRI.

Event-related BOLD fMRI data is modeled as a linear time-invariant system. Together with Bayesian inference techniques, a statistical test is developed for rigorously detecting linearity/nonlinearity in the BOLD response system. The test is applied to data collected from eight subjects using an event-related paradigm with a switching checkerboard as the visual stimulus. Analyzed as a group, the results clearly find the response to be nonlinear. When each subject is analyzed individually, however, the results are predominantly nonlinear, but there is some evidence to suggest that there may be a crossover from a linear to a nonlinear regime and vice versa. This could be important when estimating physiological parameters for individuals. Additionally, estimates of the hemodynamic response function and corresponding response were obtained, but there was no consistent appearance of a poststimulus undershoot in the event-related BOLD response.

Adult↗

Arterial fraction of cerebral blood volume in humans measured by positron emission tomography.

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.

Adult↗

Quantitative and temporal relationship between local cerebral blood flow and neuronal activation induced by somatosensory stimulation in rats.

In many studies on functional neuroimaging, change in local cerebral blood flow induced by sensory stimulation (evoked LCBF) is used as a marker for change in cortical neuronal activity, although a full description of the relationship between the evoked LCBF and neuronal activity has not been given. The purpose of this study was to estimate the close relationship between the evoked LCBF and neuronal activity. We measured the field potential using an electrode inserted into the cortex and the evoked LCBF using Laser-Doppler flowmetry in alpha-chloralose-anesthetized rats during somatosensory stimulation. Activation of the cortex was carried out by electrical stimulation of the hind paw with 1.5 mA pulses (0.1 ms) applied at the frequencies of 0.2,1,5 and 10 Hz for a 5 s duration, and at the frequencies of 1 and 5 Hz for 2,5 and 15 s durations. The response magnitude of the evoked LCBF reached the maximum at 5 Hz. During the 5 s stimulation, the pattern of change in the response magnitude of evoked LCBF to various frequencies reflected the integrated amplitude of field potentials. During the 15 s stimulation, the evoked LCBF at 5 Hz exhibited an initial peak followed by a plateau phase, although there was no initial peak at 1 Hz. These changes in evoked LCBF during the 15 s stimulation reflected change in field potentials, but they were delayed during the temporal change in field potentials. These results suggest that the response of evoked LCBF reflects the integrated neuronal activity during the stimulation period, and it is modulated by a temporal slow function.

Action Potentials↗

Hemodynamics of local cerebral blood flow induced by somatosensory stimulation under normoxia and hyperoxia in rats.

We observed changes in the local cerebral blood flow (LCBF), red blood cell (RBC) concentration and RBC velocity in alpha-chloralose anesthetized rats using laser-Doppler flowmetry during activation of the somatosensory cortex following electrical stimulation of the hind paw under hyperoxia (PaO(2)=513.5+/-48.4 mmHg; mean+/-S.D.) and normoxia (PaO(2)=106.4+/-8.4 mmHg). Electrical stimuli of 5 and 10 Hz (pulse width 0.1 ms) with an intensity of 1.5 mA were applied for 5 s (n=13 at 5 Hz, n=9 at 10 Hz). Baseline levels of LCBF and RBC concentration under hyperoxia were, respectively, 5.6+/-3.3 and 8.8+/-3.0% lower than those under normoxia (P<0.05), and that of RBC velocity under hyperoxia was slightly higher than that under normoxia (NS), suggesting mild vasoconstriction at rest under hyperoxia. At 5 Hz stimulation, after normalization to each baseline level, normalized response magnitudes of LCBF, RBC concentration and RBC velocity under hyperoxia were, respectively, 68.2+/-48.0, 71.1+/-65.5 and 66.0+/-56.3% greater than those under normoxia (P<0.05). At 10-Hz stimulation, normalized response magnitudes of LCBF and RBC concentration under hyperoxia were, respectively, 44.6+/-32.0 and 55.9+/-43.5% greater than those under normoxia (P<0.05), although a significant difference in the normalized response magnitude of RBC velocity was not detected between both conditions. The evoked LCBF under hyperoxia increased earlier, by approximately 0.15 s, than that under normoxia regardless of the stimulus frequency (P<0.05). These results suggest the involvement of oxygen interaction on the regulation of LCBF during neuronal activation.

Animals↗

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.

Adult↗

Frequency dependence of local cerebral blood flow induced by somatosensory hind paw stimulation in rat under normo- and hypercapnia.

We measured the field potential and the changes in local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in alpha-chloralose--anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO(2)=34.3+/-3.8 mmHg) and hypercapnia (PaCO(2)=70.1+/-9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1, and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2% higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2 to 5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO(2) level. The peak time and termination time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia, compared with those under normocapnia (p<0.05), although the rise time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.

Animals↗

Changes in red blood cell behavior during cerebral blood flow increase in the rat somatosensory cortex: a study of laser-Doppler flowmetry.

The purpose of this study was to investigate red blood cell (RBC) behavior during an increase in local cerebral blood flow (LCBF). We measured changes in RBC behavior by using laser-Doppler flowmetry (LDF) in alpha-chloralose-anesthetized rats. An increase in LCBF was carried out by approximately 2.5 and 4.0% CO(2) inhalation and activation of the somatosensory cortex. The activation of the cortex was induced by electrical stimulation of the hind paw with 1.5-mA pulses (0.1 ms) applied at frequencies of 0.2, 1, 5, and 10 Hz for a 5 s duration. The increases in LCBF and RBC velocity during both CO(2) inhalations were larger than that in RBC concentration (p < 0.05). LCBF and RBC velocity during 4.0% CO(2) inhalation were larger than those during 2.5% CO(2) inhalation (p < 0.05), though there was no significant difference in RBC concentration between the two conditions, suggesting a limitation of capillary volume. During somatosensory stimulation, the evoked LCBF increased with increasing stimulus frequency up to 5 Hz and decreased at 10 Hz. The responses of RBC concentration at 0.2 and 10 Hz were greater than those of RBC velocity (p < 0.05), but no significant differences in response magnitude were found at 1 and 5 Hz between RBC concentration and RBC velocity. These results suggest that the increase in LCBF during neuronal activity is different from that of controlling the LCBF as induced by CO(2), and that the regulation of RBC concentration and RBC velocity is controlled by independent mechanisms.

Animals↗

A sealed cranial window system for simultaneous recording of blood flow, and electrical and optical signals in the rat barrel cortex.

We have developed a new sealed cranial window technique which allows the manipulation of simultaneously and independently multiple sensor probes, such as a glass microelectrode and a laser-Doppler probe. possible. Furthermore, normal intracranial pressure (4 mmHg) can be maintained throughout the craniectomy and the experiment. Using this technique, we have measured the neuronal activity and local cerebral blood flow together with the intrinsic optical properties in the rat barrel cortex during mechanical stimulation of the whiskers. The onset of the field response recorded by an extracellular electrode in the principal barrel columns occurred about 8 ms from the beginning of stimulation. These responses were well correlated with the whisker displacements (3 Hz, 2 s). The local cerebral blood flow, measured by laser-Doppler flowmetry, started to increase about 0.5 s after the first field response, peaked at about 1.7 s, and then gradually waned. A similar time-course of changes in the local blood volume was observed by simultaneous intrinsic optical imaging at the hemoglobin-isosbestic wavelength (570 nm). These results suggest that our technique would be useful for assessing the mechanism underlying neurovascular coupling under physiological conditions in vivo.

Animals↗

Hyperoxia-enhanced activation-induced hemodynamic response in human VI: an fMRI study.

The effect hyperoxia had on the hemodynamic response to visual stimulation (black and white checkerboard alternating at a frequency of 8 Hz) of human VI was investigated using a blood oxygenation level-dependent (BOLD) contrast with an fMRI technique. Data were acquired with a 5 on/5 off block paradigm using single-shot gradient-echo echo-planar imaging. Using a two-tailed paired t-test (p < 0.05, n = 13) it was found that the mean percentage signal change and the mean number of activated pixels was significantly increased for hyperoxia (5.7 +/- 0.9, 187 +/- 73, mean +/- SD) relative to those for normoxia (5.4 +/- 0.9, 168 +/- 58). We believe that these results indicate that hyperoxia enhances the activation-induced hemodynamic response in human VI.

Adult↗

Evoked local cerebral blood flow induced by somatosensory stimulation is proportional to the baseline flow.

The purpose of this study was to determine the relationship between the increase in local cerebral blood flow during neuronal activation (evoked LCBF) and the baseline flow level. We measured the hemodynamics in alpha-chloralose-anesthetized rats using laser-Doppler flowmetry during somatosensory stimulation under the hypocapnic, normocapnic and hypercapnic conditions. The baseline levels of LCBF and red blood cell (RBC) velocity under hypocapnia (PaCO(2)=26.4+/-1.1 mmHg) were, respectively, 10 and 11% lower than those under normocapnia (PaCO(2)=34.2+/-1.4 mmHg) (P<0.01). The evoked response magnitude of LCBF and RBC velocity under hypocapnia were, respectively, 22 and 18% lower than those under normocapnia. There was no significant difference in the baseline level and evoked response magnitude of RBC concentration. On the other hand, the baseline levels of LCBF, RBC velocity and RBC concentration under hypercapnia (PaCO(2)=73.4+/-13.3 mmHg) were, respectively, 47, 24 and 14% higher than those under normocapnia (PaCO(2)=34.7+/-2.5 mmHg) (P<0.01). The evoked response magnitude of LCBF, RBC velocity and RBC concentration under hypercapnia were, respectively, 96, 82 and 62% greater than those under normocapnia. After normalization with respect to each baseline level, there was no significant difference in normalized evoked response magnitude of LCBF, RBC velocity and RBC concentration, either between hypocapnic and normocapnic conditions or between hypercapnic and normocapnic conditions, indicating that evoked LCBF is proportional to the baseline flow. These results suggest that the amount of evoked LCBF is not determined by the demand for metabolic substrates.

Animals↗

Regional differences in cerebral vascular response to PaCO2 changes in humans measured by positron emission tomography.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.

Aged↗

Modulation of evoked cerebral blood flow under excessive blood supply and hyperoxic conditions.

We measured the field potential and local cerebral blood flow (LCBF) using laser-Doppler flowmetry in alpha-chloralose anesthetized rats during activation of the somatosensory cortex by electrical stimulation of the hind paw under independent administration of additional carbon dioxide and oxygen. The aim of this study was to test the hypothesis that the increase in LCBF during activation of the cortex (evoked LCBF) is not directed toward supplying oxygen for oxidative metabolism. Under the hypercapnic condition (PaCO(2) = 74. 9 +/- 14.3 mmHg), the baseline LCBF was about 46.5% higher than that under the normocapnic condition (PaCO(2) = 35.7 +/- 2.1 mmHg) (p < 0. 001), but after normalization for each baseline (divided by the prestimulus level), there was no significant difference in the peak value and the rise time of normalized evoked LCBF. On the other hand, the baseline level of LCBF under the hyperoxic condition (PaO(2) = 479.4 +/- 77.2 mmHg) was about 5.0% lower than that under the normoxic condition (PaO(2) = 105.5 +/- 7.8 mmHg) (p < 0.01), suggesting mild vasoconstriction under the condition of hyperoxia at rest. The peak value of normalized evoked LCBF under the hyperoxic condition was about 6.5% higher than that under the normoxic condition (p < 0.05). In addition, the rise time of evoked LCBF was earlier under the hyperoxic condition (0.37 +/- 0.16 s) than that under the normoxic condition (0.52 +/- 0.12 s) (p < 0.01). The field potential measured during stimulation under hypercapnic and hyperoxic conditions was not significantly different when compared with that under normal gas conditions. These results support our hypothesis and suggest that the excess oxygen is involved in the mechanism underlying the regulation of LCBF.

Action Potentials↗

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage.

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.

Acute Disease↗

Verb generation in Japanese--A multicenter PET activation study.

Cerebral blood flow (CBF) during silent verb generation was measured at four Japanese PET centers. To minimize the variance of the measurement, speakers of a single language (Japanese) served as subjects and experimental conditions at the four PET centers were controlled as much as possible. Two types of activation patterns were observed: activations in the left dorsolateral prefrontal cortices and the medial frontal cortex (at the two centers with a 2D PET scanner) and additional activation in the left posterior temporal cortex (at the two centers with a 3D scanner). This suggests either a difference in the sensitivity of the two types of PET scanners (viz., a 3D scanner is generally more sensitive than a 2D scanner) and/or subject bias due to the small number of subjects at the individual centers. The pooled activation pattern was fundamentally similar to activation patterns obtained in the previous studies for verb generation in English and other European languages, suggesting that regions for verb generation are independent of particular languages. Regions relevant to verb generation are discussed.

Adult↗

Synthesis and autoradiographic localization of muscarinic cholinergic antagonist (+)N-[11C]methyl-3-piperidyl benzilate as a potent radioligand for positron emission tomography.

(+)N-[11C]methyl-3-piperidyl benzilate, a relatively low affinity muscarinic cholinergic receptor antagonist was synthesized by N-[11C]methylation of (+)3-piperidyl benzilate using [11C]methyl iodide. The product was isolated by HPLC, and obtained with radiochemical yield of 60-70% from [11C]methyl iodide, and a specific activity of 500-1000 Ci mmol-1 (18.5-37 GBq mumol-1) at EOS and radiochemical purity of > 98%. In vitro autoradiographic studies showed selective binding for this radiotracer in the different regions of the rat brain: high in corpus striatum, hippocampus and cerebral cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. This radiotracer thus had potential as radioligand for positron emission tomography.

Animals↗