N Yamaguchi

Louisiana State University Health Sciences Center New Orleans, New Orleans, Louisiana, United States

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Publications (16)34.79 Total impact

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    ABSTRACT: Pathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method. Subarachnoid hemorrhage was induced in C57Bl/6J mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna. SAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model. SAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.
    Neurosurgery 04/2009; 64(3):546-53; discussion 553-4. · 2.53 Impact Factor
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    ABSTRACT: Angiotensin II type 1 (AT(1)) receptor signaling has been implicated in cerebral microvascular alterations associated with ischemia, diabetes mellitus, hypercholesterolemia, and atherosclerosis. Platelets, which express AT(1) receptors, also appear to contribute to the thrombogenic and inflammatory responses that are elicited by these pathological conditions. This study assesses the role of AT(1) receptor activation on platelet-leukocyte-endothelial cell interactions elicited in cerebral microvasculature by ischemia and reperfusion. Intravital microscopy was used to monitor the adhesion of platelets and leukocytes that were labeled with different fluorochromes, whereas dihydrorhodamine-123 was used to quantify oxygen radical production in cerebral surface of mice that were either treated with the AT(1) receptor agonist Val-angiotensin II (ANG II) or subjected to bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. ANG II elicited a dose- and time- dependent increase in platelet-leukocyte-endothelial cell interactions in cerebral venules that included rolling platelets, adherent platelets on the leukocytes and the endothelial cells, rolling leukocytes, and adherent leukocytes. All of these interactions were attenuated by treatment with either P-selectin or P-selectin glycoprotein ligand 1 (PSGL-1) antibody. The AT(1) receptor antagonist candesartan and losartan as well as diphenyleneiodonium, an inhibitor of flavoproteins including NAD(P)H oxidase, significantly reduced the platelet-leukocyte-endothelial cell interactions elicited by either ANG II administration or BCCAO/reperfusion. The increased oxygen radical generation elicited by BCCAO/reperfusion was also attenuated by candesartan. These findings are consistent with an AT(1) receptor signaling mechanism, which involves oxygen radical production and ultimately results in P-selectin- and PSGL-1-mediated platelet-leukocyte-endothelial cell interactions in the cerebral microcirculation.
    AJP Heart and Circulatory Physiology 06/2007; 292(5):H2306-15. · 4.01 Impact Factor
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    ABSTRACT: Adenosine (ADO) has an important role in the ischemic brain as an endogenous neuroprotective factor. On the other hand, intraischemic hypothermia ameliorates ischemic neuronal injury. To investigate the effect of ADO during intraischemic mild hypothermia, the extracellular concentration of ADO, its metabolites, dopamine (DA), and local cerebral blood flow were measured in rat striatum during and after 20 min of global ischemia. Additionally, the histopathological outcome was estimated after 48 h of recirculation. Three experimental groups were used: (1) a normothermic group (NT) maintained at 37 degrees C during and after ischemia; (2) a hypothermic group (HT), exposed to intraischemic hypothermia (32.0 degrees C) and postischemic normothermia; and (3) a hypothermia plus theophylline group (HT+T), with the same temperature conditions as in the HT group, combined with intravenously administration of theophylline (10 mg/kg), an antagonist of adenosine receptor, which was given 10 min before ischemia. The level of ADO in HT was significantly higher than ADO levels in NT. In contrast, ischemic DA release was significantly inhibited in HT compared with NT. Theophylline administration had no effect on intraischemic hypothermia induced modulation of extracellular ADO and DA concentration. The postischemic delayed hypoperfusion was ameliorated in HT, and theophylline eliminated this effect in HT+T. A protective effect on histopathological outcome was observed in HT and HT+T. These results suggest that ADO plays an essential role in the inhibition of postischemic delayed hypoperfusion, but this effect is not crucial role in the protective effect induced by intraischemic hypothermia.
    Brain Research 11/2002; 952(2):222-31. · 2.88 Impact Factor
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    ABSTRACT: The mechanism of cerebral infarction, in which thrombus formation and platelet-endothelium interaction play an important part, have not yet been clearly elucidated in vivo. The aim of this study was to observe rolling and adherent platelets and to analyze adherent leukocytes and vessel diameter change in vivo using a photothrombotic vessel occlusion model.A photothrombosis, which is mediated by free radicals, was induced in male Wistar rats in the presence of a photosensitizing dye (Photofrin II) and exposure to a filtered light. Rhodamine 6G-labeled platelets and leukocytes were visualized with intravital fluorescence videomicroscopy through a closed cranial or spinal window. The vessel diameter, photothrombosis and leukocyte adhesion were analyzed. Rolling and adherent platelets were observed during irradiation through the cerebral and spinal window. Before the platelets were recognized, the irradiated arteriole dilated significantly. After the photochemical occlusion of an arteriole, other arterioles also dilated and the adherent leukocytes increased in the venules. The photothrombosis were almost completely composed of platelets according to electron microscopic analysis. The arteriolar dilation rate and the number of adherent leukocytes in the cerebrum were greater than those in the spinal cord. By combining the photochemical thrombus formation and the fluorescence microscope techniques, we were able for the first time to observe rolling and adherent platelets and microvascular responses during photothrombosis in the cerebral and spinal microvasculature. It is suggested that free radicals, which can lead to platelet aggregation, play an important role as a cerebral vasodilator. This model is useful for cerebral and spinal microcirculatory analysis to investigate the platelet-endothelium interaction, the platelet aggregation and the effect of free radicals on cerebral and spinal microcirculation.
    Journal of the Neurological Sciences 03/2002; 194(1):59-69. · 2.24 Impact Factor
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    ABSTRACT: Intravenous infusion of glycerol has been used in patients with a cerebral infarction, expecting improvement in brain edema and cerebral blood flow (CBF). However, the mechanism of the improvement of CBF has not been clearly demonstrated. The aim of this study in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO) is to examine the effects of glycerol on leukocyte-endothelium interaction, which plays a critical role in the pathogenesis of brain injury by ischemia/reperfusion and concerns induction of secondary brain damage. Rhodamine 6G-labeled leukocytes at the brain surface were visualized with intra-vital fluorescence videomicroscopy through a closed cranial window and an analysis was made of the number of adherent leukocytes and the centerline leukocyte velocity in the venule before MCAO, after reperfusion of MCAO and after infusion of glycerol (Group 1) or saline (Group 2). The number of adherent leukocytes decreased and the centerline leukocyte velocity increased statistically significantly immediately after the infusion of glycerol in Group 1, but there was no significant change in Group 2. The infusion of glycerol washes away the adherent leukocytes and prevents them from interfering with the blood cell and plasma flow. Furthermore, secondary brain damage may be relieved by decreasing the adherence of leukocytes. In conclusion, modulating the adherence of leukocytes is one of the important factors in the neuroprotective effect of glycerol.
    Neurological Research 01/2000; 21(8):785-90. · 1.18 Impact Factor
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    ABSTRACT: Background and Purpose--It has been demonstrated that moderate hypothermia attenuates brain damage, but the mechanism whereby this is achieved has not been clearly shown. Recently, the role of leukocytes as mediators of secondary brain damage after brain ischemia has been discussed. The aim of this study is to examine the effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO). Methods--Rhodamine 6G-labeled leukocytes in brain surface were visualized with intravital fluorescence videomicroscopy through a closed cranial window. We analyzed the number of leukocytes adhering to the venular and arteriolar endothelium before ischemic insult and up to 3 hours after reperfusion. Rats were divided into 4 experimental groups. Group I (n=6) consisted of sham-operated animals. Groups II (n=6) and III (n=6) received left MCAO for 1 hour under normothermia (36 degrees C to 37 degrees C, group II) and under moderate hypothermia (30 degrees C to 32 degrees C, group III). Group IV (n=4) received left common carotid artery occlusion for 1 hour under normothermia. Results--The number of adhering leukocytes in venules in groups II and IV increased significantly (P<0.001) after reperfusion compared with the group I, but that in group III did not increase significantly (P>0.05). The number of adhering leukocytes in arterioles in group II increased significantly (P<0.01) compared with the other groups, although the adhering leukocytes were not as numerous as those seen in venules. Conclusions--It is demonstrated that hypothermia attenuates adhering leukocytes in venules and arterioles after reperfusion of MCAO. The inhibition of the leukocyte function may be an important factor in the neuroprotective effect of hypothermia.
    Stroke 09/1999; 30(8):1679-86. · 6.16 Impact Factor
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    ABSTRACT: An in vivo closed spinal window technique in rats was designed for observing the spinal microcirculation, such as the change of vessel diameter, leukocyte adhesion, and red blood cell (RBC) velocity, which has been very rarely examined in vivo in the spinal cord. We made a very precise closed spinal window with a laminectomy at the C5 level using a dental acrylic resin and a cover glass (7 mm in diameter). Through this closed window, the dorsal surface of the rat cervical cord was observed with a video microscope, and the fluorescent images of rhodamine 6G-labeled leukocytes and fluorescein isothiocyanate-labeled RBCs were recorded and analyzed with a silicon-intensified target tube camera (30 frames/s) and an image-intensified high-speed video camera system (1000 frames/s). During CO2 inhalation, the pial arterioles responded with vasodilation of 12.4+/-10.4% (P<0.01) in 11 arterioles of seven rats. The adhering leukocytes significantly increased in 41 venular segments of seven rats after superfusion of the neutrophil chemoattractant, N-formyl-methionine-leucine-phenylalanine solution for 15 minutes (P<0.001) but not after superfusion of only artificial cerebrospinal fluid for 15 minutes. During these experiments, no adhering leukocyte was seen in the pial arterioles. Fluorescein isothiocyanate-labeled RBCs look like shooting stars in arterioles with silicon-intensified target tube camera processing at 30 frames per second, but individual fluorescein isothiocyanate-labeled RBCs could be recognized frame by frame with the image-intensified high-speed video camera system. In 13 arterioles of four rats, the RBC velocity was 5.3+/-2.0 mm per second. This closed spinal window technique in rats is available and applicable for the study of the spinal microcirculation, such as the pathophysiology of a secondary injury.
    Neurosurgery 01/1999; 44(1):156-61; discussion 161-2. · 2.53 Impact Factor
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    ABSTRACT: The mean centerline red blood cell (RBC) velocity of the rat pial artery was measured using an image-intensified high-speed (1000 frames/s) video camera system and RBCs labeled with fluorescein isothiocyanate (FITC). Some investigations measuring RBC velocity have been made in most organs, but the RBC velocity of the pial artery has not yet been measured with this system using FITC labeled RBC. After recording the emission of the FITC labeled RBC through a closed cranial window using this system, the authors analyzed the videotape. The movement of each individual RBC for several milliseconds over a distance of 50 μm could be pursued. The mean centerline RBC velocity in normal rats varied between 1.0 and 9.0 mm/s (most of the measurements we taken in vessels ranging between 20 and 80 μm in diameter). As the diameter of the pial artery becomes smaller, the blood flow rate (π × (diameter/2)2× (mean centerline velocity/1.6)) tends to become smaller. During CO2inhalation, the pial artery diameter, mean centerline RBC velocity, and blood flow rate increased with statistical significance. Mean centerline RBC velocities in the cerebral microcirculation could not be measured directly with accuracy using the older methods (30 frames/s). However, this method is useful for investigation of the cerebral microcirculation and is considered to be applicable for studying the behavior of leukocytes or platelets, which will be examined in a subsequent study.
    Microvascular Research 12/1998; · 2.93 Impact Factor
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    ABSTRACT: The consistency of a meningioma is one of the important factors in determining the surgical outcome. If the surgeon is aware of the consistency of a meningioma preoperatively, the surgical plans will be influenced. A few papers have described the correlation between consistency of meningiomas and their magnetic resonance imaging (MRI) findings. However, prediction of consistency with MRI is still difficult. We have tried to predict the consistency of meningiomas with MRI findings more precisely. Fifty patients diagnosed as having intracranial meningiomas were studied with 1.5 Tesla MRI. We compared the MRI findings with tumor consistency. The intensities of the tumors were categorized into three grades (low, iso, and high) compared to that of the gray matter. T1-weighted images had no specifics, but T2-weighted images and proton density images were useful for the prediction of tumor consistency. Hyperintensity on protein density (PD) and T2-weighted images was a sign of a soft tumor. We presume that T2 and PD are useful for predicting consistency of meningiomas, and their water content is one of the main factors in their consistency. Histology may be one of the factors helpful in defining the consistency of a tumor. In this series, we found no relationship between histology and MRI findings, nor between histology and consistency. If the meningioma is believed to be hard, preoperative endovascular embolization is beneficial, which will induce necrosis of the meningioma and make it soft enough to be removed more easily and safety.
    Surgical Neurology 01/1998; 48(6):579-83. · 1.67 Impact Factor
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    ABSTRACT: Refractory periods and recovery curves have been used to investigate the physiologic importance and disturbance of peripheral nerves, but the refractory periods of the central nervous system (CNS) have seldom been investigated. We estimated the refractory periods and the recovery curves of the ascending and descending conductive spinal cord evoked potentials (SCEP) in cats. The absolute refractory period of the first and second potentials of both the ascending and descending SCEP was approximately 0.4-0.5 ms. The amplitudes of the first potentials of the ascending and descending SCEP elicited by test stimuli exhibited significant differences, but their latencies did not differ significantly except at the interstimulus interval (ISI) of 1.5 ms, which implies that the same type of fibers was stimulated in the first potentials of the ascending and descending SCEP. The second potential of the descending SCEP elicited by test stimulus showed > 100% amplitude and a maximal recovery of 200% when the ISI was 3.0 ms. The third potential was produced in the test response more easily when a lower vertebral level (L4) was used as the recording site and the ISI was between 1.0 and 4.0 ms. We consider these phenomena to be the result of elimination of the synaptic inhibitory influence by the conditioning stimulus of the paired stimuli for the descending SCEP.
    Journal of Clinical Neurophysiology 07/1997; 14(4):335-44. · 1.45 Impact Factor
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    ABSTRACT: This study was designed to examine the possibility of a new spinal cord monitoring method using measurement of the refractory period to monitor spinal cord function. To determine whether measuring the refractory period and the recovery rate of conductive spinal cord evoked potential is a useful method for estimating spinal cord function. Measuring the refractory period and constructing the recovery curve have been used to investigate peripheral nerve function. Spinal cord evoked potential elicited by the single stimulus usually is used to evaluate spinal cord function, and it has been said that 50% attenuation of the amplitude is the critical alarm level. In anesthetized cats, amplitude, area, and latency were measured on a personal computer from subtracted data collected with a paired-stimulation technique. The authors constructed recovery curves of ascending and descending conductive spinal cord evoked potentials and measured the refractory period during spinal cord compression. When the amplitude of the ascending spinal cord evoked potential began to decrease during spinal cord compression, the amplitude of the response elicited by the second stimulus with interstimulus intervals of 0.8 msec and 1.0 msec decreased more significantly. When the amplitude of the ascending spinal cord evoked potential decreased to 50% of the precompression amplitude, the mean value of the absolute refractory periods of the ascending and descending spinal cord evoked potentials became prolonged from 0.40 +/- 0.007 msec to 0.53 +/- 0.014 msec, and the mean values of their amplitude and area recovery rates decreased from 75% +/- 1% to 35% +/- 2% (interstimulus interval, 0.8 msec) and from 81% +/- 1% to 46% +/- 2% (insterstimulus interval, 1.0 msec). The change of the responses elicited by the paired stimuli is more sensitive than those elicited by the single stimulus in the spinal cord evoked potentials. The absolute refractory periods and the recovery rate during 50% attenuation of the precompression amplitude is the critical alarm level in spinal cord monitoring.
    Spine 06/1997; 22(9):1007-12. · 2.16 Impact Factor
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    ABSTRACT: The recovery cycle, following the conduction of action potentials along a nerve fiber, consists of the absolute refractory period (ARP), the relative refractory period (RRP) and the supernormal period (SNP). The recovery cycle of the descending conductive spinal cord evoked potential (SCEP) was shown during normal state, ischemia and after ischemia using paired stimuli in cats. During ischemia the refractory period revealed a trend towards increment. Five minutes after reperfusion the refractory period decreased transiently compared with the normal level and within 30 min the refractory period returned to the normal level. The recovery curve of the 2nd potential showed different pattern compared with that of the 1st potential. Moreover, during ischemia, firstly the 3rd potential and secondly the 2nd potential of the SCEP elicited by the 2nd stimulus were disturbed. These results demonstrated that there is increased excitability of the spinal cord to the second stimulus after a brief period of ischemia, and that the 2nd and 3rd potentials are evoked synaptically and easily disturbed during ischemia. Measuring the SCEP elicited by paired stimuli or constructing the recovery curve of the SCEP is useful for the electrophysiological assessment of spinal cord function.
    Electroencephalography and Clinical Neurophysiology 02/1997; 102(1):54-63.
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    ABSTRACT: Strength-duration curves of the ascending and descending conductive spinal cord potentials (SCEPs) in cats were obtained using constant current stimuli. For the formulation of numeric indices of excitability, the rheobase is defined as the minimal current strength below which response cannot occur even if the current continues, and the chronaxie is defined as the minimal duration of a current required to evoke the potential at twice the rheobase strength. The chronaxies and rheobases were calculated from the constructed strength-duration curves. The purpose of this study is to produce strength-duration curves and to evaluate the utility of chronaxies and rheobases for SCEPs. This study showed the following results: (1) there was a hyperbolic relationship between stimulus strength and stimulus duration at threshold values, similar to that seen in peripheral nerves; (2) the ascending and descending tracts of SCEP were mediated through the same pathway (based on the similar chronaxies and rheobases); (3) following spinal cord compression the chronaxie and rheobase increased significantly (P < 0.05), which is similar to peripheral nerve disturbance. However, the rheobase decreased significantly following slight spinal cord compression (P < 0.05) and systemic cooling (P < 0.01), and the strength-duration curve shifted showing a tendency towards decrease of the galvanic threshold, therefore, amplitude augmentation with slight compression and with decrease in temperature seems to contribute to the reduction of the threshold. The strength-duration curve, the chronaxie and the rheobase may be useful in assessing spinal cord function.
    Electroencephalography and Clinical Neurophysiology 05/1996; 100(3):261-8.
  • N Yamaguchi, H Miyazaki, N Ishiyama, S Toya
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    ABSTRACT: A 41-year-old male presented with vertigo, nausea, and vomiting suggesting a space-occupying lesion of the posterior fossa. Computed tomography (CT) and left vertebral angiography revealed a large distal posterior inferior cerebellar artery (PICA) aneurysm. Operation revealed the fusiform aneurysm was partially embedded in the medulla, preventing neck clipping or trapping of the aneurysm. Therefore, proximal ligation of the PICA was performed. The symptoms caused by the mass effect improved, and the aneurysm was not visualized by CT or angiography. Ligation of the PICA proximal to the choroidal point is not necessarily safe. In our case, ligation was distal to the tonsillomedullary segment from which the perforating arteries mainly arose, so the postoperative course was good without new neurological deficits. Proximal ligation is an effective treatment for distal PICA aneurysms manifesting as mass effect if other interventions are not possible.
    Neurologia medico-chirurgica 02/1996; 36(1):31-5. · 0.49 Impact Factor
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    ABSTRACT: A new experimental model is described that uniquely allows the in vivo observation and quantification of vascular caliber changes on the dorsal surface of the feline spinal cord. The model consists of a rectangular Plexiglas window that is sutured to the lumbar dura and is supported by a special holder. Inlet and outlet tubes attached to the window serve for topical applications of mock cerebrospinal fluid or vasoactive agents to the surface of the cord and for continuous monitoring of intrathecal pressure. Pial vessels below the window were observed at 200-fold magnification with the aid of a microvideo camera. Spinal arterioles reacted to hypercarbia and superfusion with acetylcholine solution in a manner similar to cerebral arterioles. Tests with increased intrathecal pressure showed that the window remained watertight between 25 and 130 mm Hg, with an average leakage pressure of 57.8 +/- 33.5 mm Hg. To promote the use of this model in other laboratories, the authors give a detailed description of the closed spinal window preparation and report their experiences gained from 50 experiments. It is concluded that the closed spinal window is a highly reproducible model, suitable for the study of the feline spinal microcirculation for several hours in vivo.
    Neurosurgery 03/1994; 34(2):316-21; discussion 322. · 2.53 Impact Factor
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    ABSTRACT: Propentofylline (HWA285) has been reported to protect neuronal cells through the inhibition of glutamate release during transient ischemia. We studied whether HWA285 inhibits dopamine (DA) release, and how HWA285 modulates DA metabolism in the rat model. HWA285 was perfused through a microdialysis probe placed in the rat striatum during 20 min transient ischemia. In rats perfused by HWA285, ischemic DA release was significantly inhibited, and DA metabolism showed better recovery in contrast with unperfused rats.
    Neuroscience Letters 09/1993; 158(1):9-12. · 2.03 Impact Factor

Publication Stats

182 Citations
34.79 Total Impact Points


  • 2002
    • Louisiana State University Health Sciences Center New Orleans
      New Orleans, Louisiana, United States
  • 1993–2002
    • Keio University
      • School of Medicine
      Tokyo, Tokyo-to, Japan
  • 1998
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1996
    • Hiratsuka City Hospital
      Hiratuka, Kanagawa, Japan