Kazuto MASAMOTO
| Department of Mechanical and Intelligent Systems Engineering | Professor |
| Cluster II (Emerging Multi-interdisciplinary Engineering) | Professor |
| Center for Neuroscience and Biomedical Engineering | Professor |
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Paper
- Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex
Wonyoung Lee; Byunghee Kang; Hyo-Min Kim; Tsuyoshi Ishida; Minkyung Shin; Misato Iwashita; Masahiro Nitta; Aki Shiraishi; Hiroshi Kiyonari; Koichiro Shimoya; Kazuto Masamoto; Tae-Young Roh; Yoichi Kosodo
The EMBO Journal, Springer Science and Business Media LLC, 44, 2, 382-412, 12 Dec. 2024, Peer-reviwed, Abstract
Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation. Acute manipulation of p18 and p27 levels shows that CDKIs modulate lineage switching between upper-layer neurons and astrocytes at the transitional stage. We generate a conditional knock-in mouse model to induce p18 in NSCs. The transcriptomic deconvolution of microdissected tissue reveals that increased levels of p18 promote glial cell development and activate Delta-Notch signaling. Furthermore, we show that p18 upregulates the homeobox transcription factor Dlx2 to subsequently induce the differentiation of olfactory bulb interneurons while reducing the numbers of upper-layer neurons and astrocytes at the perinatal stage. Clonal analysis using transposon-based reporters reveals that the transition from the astrocyte to the interneuron lineage is potentiated by p18 at the single-cell level. In sum, our study reports a function of p18 in determining the developmental boundaries among different cellular lineages arising sequentially from NSCs in the dorsal cortex.
Scientific journal, English - Microfluctuations in Capillary Lumens Independent of Pericyte Lining Density in the Anesthetized Mouse Cortex
Hiroki Suzuki; Juri Murata; Miyuki Unekawa; Iwao Kanno; Yoshikane Izawa; Yutaka Tomita; Kenji F. Tanaka; Jin Nakahara; Kazuto Masamoto
Last, Microcirculation, Wiley, 16 Sep. 2024, ABSTRACT
Objective
This study aimed to examine the spatiotemporal coherence of capillary lumen fluctuations in relation to spatial variations in the pericyte lining in the cortex of anesthetized mice.
Methods
Two‐photon microscopic angiography data (previously published) were reanalyzed, and spatial variations in capillary diameter fluctuations at rest and in capillary lining with vascular mural cells were measured along capillary centerlines.
Results
Relatively large diameters of the capillaries (5.5 μm) coincided with a dense pericyte lining, while small capillaries (4.3 μm) had a sparse pericyte lining. Temporal variations had a frequency of about 0.1 Hz with an amplitude of 0.5 μm, which were negatively correlated with pericyte lining density. Spatial frequency analysis further revealed a common pattern of spatial variations in capillary diameter and pericyte lining, but temporal variations differed. The temporal variations in capillary lumens were locally distinct from those in neighboring locations, suggesting intrinsic fluctuations independent of the pericyte lining.
Conclusions
Capillary lumens in the brain exhibit slow microfluctuations that are independent of pericyte lining. These microfluctuations could affect the distribution of flowing blood cells and may be important for homogenizing their distribution in capillary networks.
Scientific journal, English - Effect of Diabetes on Microvascular Morphology and Permeability of Rat Skeletal Muscle: In Vivo Imaging Using Two-Photon Laser Scanning Microscopy
Kazuki Hotta; Rie Shimotsu; Bradley J. Behnke; Kazuto Masamoto; Kazuyoshi Yagishita; David C. Poole; Yutaka Kano
Journal of Applied Physiology, American Physiological Society, 15 Aug. 2024, This investigation evaluated the microvascular permeability and ultrastructure of skeletal muscle capillaries in skeletal muscle of diabetic (DIA) rats using two-photon laser scanning microscopy (TPLSM) and transmission electron microscopy (TEM). Microvascular permeability was assessed in the tibialis anterior muscle of control (CON) and DIA (streptozocin) male Wistar rats (n = 20, 10-14 wk) by in vivo imaging using TPLSM after fluorescent dye intravenous infusion. Fluorescent dye leakage was quantified to determine microvascular permeability. The ultrastructure was imaged by TEM ex vivo to calculate the size and number of intercellular clefts between capillary endothelial cells and also intracellular vesicles. Compared with control, the volumetrically determined interstitial fluorescent dye leakage, the endothelial cell thickness, and the number of intercellular clefts per capillary perimeter were significantly higher, and the cleft width was significantly narrower in TA of DIA (interstitial fluorescent dye leakage, 2.88 ± 1.40 vs. 10.95 ± 1.41 µm3 x min x 106; endothelial thickness 0.28 ± 0.02 vs. 0.45 ± 0.03 µm; number of intercellular clefts per capillary perimeter 6.3 ± 0.80 vs. 13.6 ± 1.7 /100 µm; cleft width 11.92 ± 0.95 vs. 8.40 ± 1.03 nm, CON vs. DIA respectively, all p <0.05). The size of intracellular vesicles in the vascular endothelium showed an increased proportion of large vesicles in the DIA group compared to the CON group (p < 0.05). Diabetes mellitus enhances the microvascular permeability of skeletal muscle microvessels, due, in part, to a higher density and narrowing of the endothelial intercellular clefts, and larger intracellular vesicles.
Scientific journal - Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice
Akiyo Natsubori; Soojin Kwon; Yoshiko Honda; Takashi Kojima; Akihiro Karashima; Kazuto Masamoto; Makoto Honda
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, 44, 9, 1591-1607, 13 Mar. 2024, Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca2+ levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT1B receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.
Scientific journal, English - Detection of backside coupled propagating surface plasmon resonance on the sidewall of a wafer
M. Oshita; S. Suzuki; K. Masamoto; T. Kan
AIP Advances, AIP Publishing, 13, 11, 01 Nov. 2023, We proposed a surface plasmon resonance (SPR) sensor structure that utilized a glass wafer with a diffraction grating and an n-type silicon piece bonded near the SPR coupling site. This configuration enabled surface plasmon excitation from the back of the substrate without the unwanted interaction between the excitation light and the sample, and electrical detection of the SPR response by a 0.7-eV Schottky barrier at the Au/n-Si interface formed on the sidewall of the silicon piece was achieved. Experimental evaluation of the surface plasmon coupling performance was conducted, showing clear peaks in the photocurrent for various wavelengths in the NIR-II window, ranging from 1100 to 1300 nm. The device’s ability to detect propagating surface plasmons as a photocurrent was confirmed; the results indicated a consistent trend with theoretical and numerical calculations. Since the device was composed of a glass substrate, the use of wavelengths shorter than the near-infrared wavelength was possible, including visible wavelengths where the optical absorption by water is negligible. Thus, our proposed sensor provides a compact and efficient solution for SPR sensing in aqueous solutions.
Scientific journal - Acceleration of the Development of Microcirculation Embolism in the Brain due to Capillary Narrowing
Juri Murata; Miyuki Unekawa; Yuya Kudo; Maho Kotani; Iwao Kanno; Yoshikane Izawa; Yutaka Tomita; Kenji F. Tanaka; Jin Nakahara; Kazuto Masamoto
Last, Stroke, Ovid Technologies (Wolters Kluwer Health), 54, 8, 2135-2144, Aug. 2023, Peer-reviwed, BACKGROUND:
Cerebral microvascular obstruction is critically involved in recurrent stroke and decreased cerebral blood flow with age. The obstruction must occur in the capillary with a greater resistance to perfusion pressure through the microvascular networks. However, little is known about the relationship between capillary size and embolism formation. This study aimed to determine whether the capillary lumen space contributes to the development of microcirculation embolism.
METHODS:
To spatiotemporally manipulate capillary diameters in vivo, transgenic mice expressing the light-gated cation channel protein ChR2 (channelrhodopsin-2) in mural cells were used. The spatiotemporal changes in the regional cerebral blood flow in response to the photoactivation of ChR2 mural cells were first characterized using laser speckle flowgraphy. Capillary responses to optimized photostimulation were then examined in vivo using 2-photon microscopy. Finally, microcirculation embolism due to intravenously injected fluorescent microbeads was compared under conditions with or without photoactivation of ChR2 mural cells.
RESULTS:
Following transcranial photostimulation, the stimulation intensity-dependent decrease in cerebral blood flow centered at the irradiation was observed (14%–49% decreases relative to the baseline). The cerebrovascular response to photostimulation showed significant constriction of the cerebral arteries and capillaries but not of the veins. As a result of vasoconstriction, a temporal stall of red blood cell flow occurred in the capillaries of the venous sides. The 2-photon excitation of a single ChR2 pericyte demonstrated the partial shrinkage of capillaries (7% relative to the baseline) around the stimulated cell. With the intravenous injection of microbeads, the occurrence of microcirculation embolism was significantly enhanced (11% increases compared to the control) with photostimulation.
CONCLUSIONS:
Capillary narrowing increases the risk of developing microcirculation embolism in the venous sides of the cerebral capillaries.
Scientific journal, English - Capillary responses to functional and pathological activations rely on the capillary states at rest
Hiroki Suzuki; Hiroshi Takeda; Hiroyuki Takuwa; Bin Ji; Makoto Higuchi; Iwao Kanno; Kazuto Masamoto
Last, Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, 43, 6, 1010-1024, 08 Feb. 2023, Peer-reviwed, Brain capillaries play a crucial role in maintaining cellular viability and thus preventing neurodegeneration. The aim of this study was to characterize the brain capillary morphology at rest and during neural activation based on a big data analysis from three-dimensional microangiography. Neurovascular responses were measured using a genetic calcium sensor expressed in neurons and microangiography with two-photon microscopy, while neural acivity was modulated by stimulation of contralateral whiskers or by a seizure evoked by kainic acid. For whisker stimulation, 84% of the capillary sites showed no detectable diameter change. The remaining 10% and 6% were dilated and constricted, respectively. Significant differences were observed for capillaries in the diameter at rest between the locations of dilation and constriction. Even the seizures resulted in 44% of the capillaries having no detectable change in diameter, while 56% of the capillaries dilated. The extent of dilation was dependent on the diameter at rest. In conclusion, big data analysis on brain capillary morphology has identified at least two types of capillary states: capillaries with diameters that are relatively large at rest and stable over time regardless of neural activity and capillaries whose diameters are relatively small at rest and vary according to neural activity.
Scientific journal, English - Close association between spreading depolarization and development of infarction under experimental ischemia in anesthetized male mice
Miyuki Unekawa; Yutaka Tomita; Kazuto Masamoto; Iwao Kanno; Jin Nakahara; Yoshikane Izawa
Brain Research, Elsevier BV, 1792, 148023-148023, Oct. 2022, Peer-reviwed
Scientific journal - Spatiotemporal analysis of blood plasma and blood cell flow fluctuations of cerebral microcirculation in anesthetized rats
Tomoya Niizawa; Ruka Sakuraba; Tomoya Kusaka; Yuika Kurihara; Takuma Sugashi; Hiroshi Kawaguchi; Iwao Kanno; Kazuto Masamoto
Last, Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, 43, 1, 138-152, 22 Sep. 2022, Peer-reviwed, Cerebral hemodynamics fluctuates spontaneously over broad frequency ranges. However, its spatiotemporal coherence of flow oscillations in cerebral microcirculation remains incompletely understood. The objective of this study was to characterize the spatiotemporal fluctuations of red blood cells (RBCs) and plasma flow in the rat cerebral microcirculation by simultaneously imaging their dynamic behaviors. Comparisons of changes in cross-section diameters between RBC and plasma flow showed dissociations in penetrating arterioles. The results indicate that vasomotion has the least effect on the lateral movement of circulating RBCs, resulting in variable changes in plasma layer thickness. Parenchymal capillaries exhibited slow fluctuations in RBC velocity (0.1 to 0.3 Hz), regardless of capillary diameter fluctuations (<0.1 Hz). Temporal fluctuations and the velocity of RBCs decreased significantly at divergent capillary bifurcations. The results indicate that a transit of RBCs generates flow resistance in the capillaries and that slow velocity fluctuations of the RBCs are subject to a number of bifurcations. In conclusion, the high-frequency oscillation of the blood flow is filtered at the bifurcation through the capillary networks. Therefore, a number of bifurcations in the cerebral microcirculation may contribute to the power of low-frequency oscillations.
Scientific journal - Automated capillary flow segmentation and mapping for nailfold video capillaroscopy
Tomoya Niizawa; Kota Yokemura; Tomoya Kusaka; Takuma Sugashi; Ichiro Miura; Keiji Kawagoe; Kazuto Masamoto
Last, Microcirculation, Wiley, 29, 3, e12753, Mar. 2022, Peer-reviwed, Abstract
Objective
This study aimed to develop an automated image analysis method for segmentation and mapping of capillary flow dynamics captured using nailfold video capillaroscopy (NVC). Methods were applied to compare capillary flow structures and dynamics between young and middle‐aged healthy controls.
Methods
NVC images were obtained in a resting state, and a region of the vessel in the image was extracted using a conventional U‐Net neural network. The approximate length, diameter, and radius of the curvature were calculated automatically. Flow speed and its fluctuation over time were mapped using the Radon transform and frequency spectrum analysis from the kymograph image created along the vessel's centerline.
Results
The diameter of the curve segment (14.4 μm and 13.0 μm) and the interval of two straight segments (13.7 μm and 32.1 μm) of young and middle‐aged subjects, respectively, were significantly different. Faster flow was observed in older subjects (0.48 mm/s) than in younger subjects (0.26 mm/s). The power spectral analysis revealed a significant correlation between the high‐frequency power spectrum and the flow speed.
Conclusions
The present method allows a spatiotemporal characterization of capillary morphology and flow dynamics with NVC, allowing a wide application such as large‐scale health assessment.
Scientific journal, English - 実験動物の画像情報に基づいた行動評価法の提案:撮像のフレームレートによる影響評価
村田樹里; 濱谷ひかる; 井上幹太; 矢野祐希; 吉田智毅; 新澤智也; 須貸拓馬; 正本和人
Last, 生体医工学, 59, 6, 139-145, Dec. 2021, Peer-reviwed
Scientific journal, Japanese - Three-dimensional microvascular network reconstruction from in vivo images with adaptation of the regional inhomogeneity in the signal-to-noise ratio
Takuma Sugashi; Hiroya Yuki; Tomoya Niizawa; Hiroyuki Takuwa; Iwao Kanno; Kazuto Masamoto
Microcirculation, John Wiley and Sons Inc, 28, 5, 01 Jul. 2021
Scientific journal, English - Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice
Yoshifumi Abe; Soojin Kwon; Mitsuhiro Oishi; Miyuki Unekawa; Norio Takata; Fumiko Seki; Ryuta Koyama; Manabu Abe; Kenji Sakimura; Kazuto Masamoto; Yutaka Tomita; Hideyuki Okano; Hajime Mushiake; Kenji F. Tanaka
Cell Reports, Elsevier BV, 36, 4, 109427-109427, Jul. 2021, Peer-reviwed
Scientific journal, English - Vascular permeability of skeletal muscle microvessels in rat arterial ligation model: in vivo analysis using two-photon laser scanning microscopy.
Rie Shimotsu; Kzuki Hotta; Ryo Ikegami; Tomoyo Asamura; Ayaka Tabuchi; Kazuto Masamoto; Kazuyoshi Yagishita; David C Poole; Yutaka Kano
American journal of physiology. Regulatory, integrative and comparative physiology, 320, 6, R972-R983, 01 Jun. 2021, Peer-reviwed, True, Peripheral artery disease (PAD) in the lower limb compromises oxygen supply due to arterial occlusion. Ischemic skeletal muscle is accompanied by capillary structural deformation. Therefore, using novel microscopy techniques, we tested the hypothesis that endothelial cell swelling temporally and quantitatively corresponds to enhanced microvascular permeability. Hindlimb ischemia was created in male Wistar rat's by iliac artery ligation (AL). The tibialis anterior (TA) muscle microcirculation was imaged using intravenously infused rhodamine B isothiocyanate dextran fluorescent dye via two-photon laser scanning microscopy (TPLSM) and dye extravasation at 3 and 7 days post-AL quantified to assess microvascular permeability. The TA microvascular endothelial ultrastructure was analyzed by transmission electron microscopy (TEM). Compared with control (0.40 ± 0.15 μm3 × 106), using TPLSM, the volumetrically determined interstitial leakage of fluorescent dye measured at 3 (3.0 ± 0.40 μm3 × 106) and 7 (2.5 ± 0.8 μm3 × 106) days was increased (both P < 0.05). Capillary wall thickness was also elevated at 3 (0.21 ± 0.06 μm) and 7 (0.21 ± 0.08 μm) days versus control (0.11 ± 0.03 μm, both P < 0.05). Capillary endothelial cell swelling was temporally and quantitatively associated with elevated vascular permeability in the AL model of PAD but these changes occurred in the absence of elevations in protein levels of vascular endothelial growth factor (VEGF) its receptor (VEGFR2 which decreased by AL-7 day) or matrix metalloproteinase. The temporal coherence of endothelial cell swelling and increased vascular permeability supports a common upstream mediator. TPLSM, in combination with TEM, provides a sensitive and spatially discrete technique to assess the mechanistic bases for, and efficacy of, therapeutic countermeasures to the pernicious sequelae of compromised peripheral arterial function.
Scientific journal, English - Error Evaluation for Automated Diameter Measurements of Cerebral Capillaries Captured with Two-Photon Laser Scanning Fluorescence Microscopy
Hiroki Suzuki; Takuma Sugashi; Hiroshi Takeda; Hiroyuki Takuwa; Iwao Kanno; Kazuto Masamoto
Last, Advances in Experimental Medicine and Biology, Springer International Publishing, 241-245, 09 May 2021, Peer-reviwed
In book, English - Time Series Tracking of Cerebral Microvascular Adaptation to Hypoxia and Hyperoxia Imaged with Repeated In Vivo Two-Photon Microscopy
Takuma Sugashi; Tomoya Niizawa; Hiroki Suzuki; Hiroyuki Takuwa; Miyuki Unekawa; Yutaka Tomita; Iwao Kanno; Kazuto Masamoto
Last, Advances in Experimental Medicine and Biology, Springer International Publishing, 323-327, 09 May 2021, Peer-reviwed
In book, English - Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons
Nao Hatakeyama; Miyuki Unekawa; Juri Murata; Yutaka Tomita; Norihiro Suzuki; Jin Nakahara; Hiroyuki Takuwa; Iwao Kanno; Ko Matsui; Kenji F Tanaka; Kazuto Masamoto
Last, Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, 41, 10, 2676-2689, 25 Apr. 2021, Peer-reviwed, A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.
Scientific journal, English - Mapping of flow velocity using spatiotemporal changes in time‐intensity curves from indocyanine green videoangiography
Tomoya Niizawa; Ryota Hachiya; Takuma Sugashi; Satoshi Terao; Mutsumi Nagai; Mami Ishikawa; Kazuto Masamoto
Last, Microcirculation, Wiley, 28, 4, e12685, 03 Mar. 2021, Peer-reviwed, Abstract
Objective
The present study developed an image‐based analysis method that uses indocyanine green videoangiography (ICG‐VA) to measure flow velocity in the arteries and veins of the cortical surface in patients undergoing neurosurgery.
Methods
MATLAB‐based code was used to correct motion artifacts in the ICG‐VA and determine the time‐intensity curve of the ICG. The slope of the initial increase in ICG intensity following the bolus injection was measured and normalized using the predicted input function in the imaging field. Flow velocity over a certain distance determined by the user was measured based on a time shift of the time‐intensity curves along the centerline of the vessels.
Results
The normalized slope of ICG intensity represented the expected differences in the flow velocity among the artery (0.67 ± 0.05 s−1), parenchymal tissue (0.49 ± 0.10 s−1), and vein (0.44 ± 0.11 s−1). The flow velocities measured along the vessel centerline were 2.5 ± 1.1 cm/s and 1.1 ± 0.3 cm/s in the arteries (0.5 ± 0.2 mm in diameter) and veins (0.6 ± 0.2 mm in diameter), respectively.
Conclusions
An image‐based analysis method for ICG‐VA was developed to map the expected differences in the flow velocity based on the rising slope of ICG intensity and to measure the absolute flow velocities using the flexible zone and cross‐correlation methods.
Scientific journal, English - Tracking tau fibrillogenesis and consequent primary phagocytosis of neurons mediated by microglia in a living tauopathy model
Hiroyuki Takuwa; Asumi Orihara; Yuhei Takado; Takuya Urushihata; Masafumi Shimojo; Ai Ishikawa; Manami Takahashi; Anna M. Barron; Maiko Ono; Jun Maeda; Kazuto Masamoto; Hiroyasu Akatsu; Aviva M. Tolkovsky; Bin Ji; Yutaka Tomita; Hiroshi Ito; Ming-Rong Zhang; Michel Goedert; Maria Grazia Spillantini; Virginia M. -Y. Lee; John Q. Trojanowski; Taketoshi Maehara; Tetsuya Suhara; Naruhiko Sahara; Makoto Higuchi
Cold Spring Harbor Laboratory, 05 Nov. 2020, ABSTRACT
Fibrillary tau pathologies have been implicated in Alzheimer’s and allied neurodegenerative diseases, while mechanisms by which neurons bearing tau tangles die remain enigmatic. To address this issue, we pursued tau and related key pathologies macroscopically by PET and MRI and microscopically by intravital two-photon laser optics. Time-course macroscopic assays of tau transgenic mice demonstrated intimate associations of tau deposition and increase of an inflammatory microglial marker, translocator protein (TSPO), with regional brain atrophy. Longitudinal microscopy of these mice revealed a rapid turnover of tau lesions resulting from continuous generation of new tau aggregates followed by loss of neurons and their fibrillar contents. This technology also allowed the capturing of the disappearance of tangle-bearing neurons several days after being engulfed by activated microglia. Notably, a therapeutic TSPO ligand profoundly suppressed the mobility and phagocytotic activity of microglia and improved neuronal survival in this model, supporting the involvement of primary phagocytosis of viable neurons by microglia in tau-primed neuronal death. Finally, partial depletion of microglia revealed roles of immune factors, MFG-E8 and C1q, as ‘eat-me’ signals for an immediate attraction of phagocytic microglia towards the elimination of tangle-loaded neurons. - Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states
Akiyo Natsubori; Tomomi Tsunematsu; Akihiro Karashima; Hiromi Imamura; Naoya Kabe; Andrea Trevisiol; Johannes Hirrlinger; Tohru Kodama; Tomomi Sanagi; Kazuto Masamoto; Norio Takata; Klaus-Armin Nave; Ko Matsui; Kenji F. Tanaka; Makoto Honda
Communications Biology, Springer Science and Business Media LLC, 3, 1, 07 Sep. 2020, Peer-reviwed, Abstract
Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.
Scientific journal, English - Neurosurgical intraoperative ultrasonography using contrast enhanced superb microvascular imaging -vessel density and appearance time of the contrast agent-
Mami Ishikawa; Kazuto Masamoto; Ryota Hachiya; Hiroshi Kagami; Makoto Inaba; Heiji Naritaka; Shojiro Katoh
British Journal of Neurosurgery, Informa UK Limited, 37, 3, 485-494, 10 Jul. 2020, Peer-reviwed
Scientific journal, English - Spatiotemporal dynamics of red blood cells in capillaries in layer I of the cerebral cortex and changes in arterial diameter during cortical spreading depression and response to hypercapnia in anesthetized mice
Miyuki Unekawa; Yutaka Tomita; Haruki Toriumi; Takashi Osada; Kazuto Masamoto; Hiroshi Kawaguchi; Yoshikane Izawa; Yoshiaki Itoh; Iwao Kanno; Norihiro Suzuki; Jin Nakahara
Microcirculation, Wiley, 26, 6, e12552, 02 Jun. 2019, Peer-reviwed, Abstract
Objective
Control of red blood cell velocity in capillaries is essential to meet local neuronal metabolic requirements, although changes of capillary diameter are limited. To further understand the microcirculatory response during cortical spreading depression, we analyzed the spatiotemporal changes of red blood cell velocity in intraparenchymal capillaries.
Methods
In urethane‐anesthetized Tie2‐green fluorescent protein transgenic mice, the velocity of fluorescence‐labeled red blood cells flowing in capillaries in layer I of the cerebral cortex was automatically measured with our Matlab domain software (KEIO‐IS2) in sequential images obtained with a high‐speed camera laser‐scanning confocal fluorescence microscope system.
Results
Cortical spreading depression repeatedly increased the red blood cell velocity prior to arterial constriction/dilation. During the first cortical spreading depression, red blood cell velocity significantly decreased, and sluggishly moving or retrograde‐moving red blood cells were observed, concomitantly with marked arterial constriction. The velocity subsequently returned to around the basal level, while oligemia after cortical spreading depression with slight vasoconstriction remained. After several passages of cortical spreading depression, hypercapnia‐induced increase of red blood cell velocity, regional cerebral blood flow and arterial diameter were all significantly reduced, and the correlations among them became extremely weak.
Conclusions
Taken together with our previous findings, these simultaneous measurements of red blood cell velocity in multiple capillaries, arterial diameter and regional cerebral blood flow support the idea that red blood cell flow might be altered independently, at least in part, from arterial regulation, that neuro‐capillary coupling plays a role in rapidly meeting local neural demand.
Scientific journal, English - Vascular Gap Junctions Contribute to Forepaw Stimulation-Induced Vasodilation Differentially in the Pial and Penetrating Arteries in Isoflurane-Anesthetized Rats
Nobuhiro Watanabe; Satoshi Sasaki; Kazuto Masamoto; Harumi Hotta
Frontiers in Molecular Neuroscience, Frontiers Media SA, 11, 446, 03 Dec. 2018, Peer-reviwed
Scientific journal, English - Optical imaging and modulation of neurovascular responses.
Masamoto K; Vazquez A
J Cereb Blood Flow Metab., 38, 12, 2057-2072, Dec. 2018, Peer-reviwed
English - Microvascular permeability of skeletal muscle after eccentric contraction-induced muscle injury: in vivo imaging using two-photon laser scanning microscopy
Kazuki Hotta; Bradley Jon Behnke; Kazuto Masamoto; Rie Shimotsu; Naoya Onodera; Akihiko Yamaguchi; David C. Poole; Yutaka Kano
Journal of Applied Physiology, American Physiological Society, 125, 2, 369-380, 01 Aug. 2018, Peer-reviwed, Via modulation of endothelial integrity and vascular permeability in response to damage, skeletal muscle microvessels play a crucial permissive role in tissue leukocyte invasion. However, direct visual evidence of altered microvascular permeability of skeletal muscle has not been technically feasible, impairing mechanistic understanding of these responses. Two-photon laser scanning microscopy (TPLSM) allows three-dimensional in vivo imaging of skeletal muscle microcirculation. We hypothesized that the regulation of microvascular permeability in vivo is temporally related to acute inflammatory and regenerative processes following muscle injury. To test our hypothesis, tibialis anterior muscles of anesthetized male Wistar rats were subjected to eccentric contractions (ECCs) via electrical stimulation. The skeletal muscle microcirculation was imaged by an intravenously infused fluorescent dye (rhodamine B isothiocyanate-dextran) to assess microvascular permeability via TPLSM 1, 3, and 7 days after ECC. Immunohistochemistry on serial muscle sections was performed to determine the proportion of VEGF-A-positive muscle fibers in the damaged muscle. Compared with control rats, the volumetrically determined interstitial leakage of fluorescent dye (5.1 ± 1.4, 5.3 ± 1.2 vs. 0.51 ± 0.14 μm3 × 106; P < 0.05, days 1 and 3, respectively, vs. control) and percentage of VEGF-A-positive fibers in the damaged muscle (10 ± 0.4%, 22 ± 1.1% vs. 0%; days 1 and 3, respectively, vs. control) were significantly higher on days 1 and 3 after ECC. The interstitial leakage volume returned to control by day 7. These results suggest that microvascular hyperpermeability assessed by in vivo TPLSM imaging is associated with ECC-induced muscle damage and increased VEGF expression.
NEW & NOTEWORTHY This investigation employed a novel in vivo imaging technique for skeletal muscle microcirculation using two-photon laser scanning microscopy that enabled microvascular permeability to be assessed by four-dimensional image analysis. By combining in vivo imaging and histological analysis, we found the temporal profile of microvascular hyperpermeability to be related to that of eccentric contraction-induced skeletal muscle injury and pronounced novel myocyte VEGF expression.
Scientific journal, English - Positron emission tomography of cerebral angiogenesis and TSPO expression in a mouse model of chronic hypoxia
Iwao Kanno; Chie Seki; Hiroyuki Takuwa; Zhao-Hui Jin; Didier Boturyn; Pascal Dumy; Takako Furukawa; Tsuneo Saga; Hiroshi Ito; Kazuto Masamoto
Last, Journal of Cerebral Blood Flow and Metabolism, SAGE Publications Ltd, 38, 4, 687-696, 01 Apr. 2018, Peer-reviwed
Scientific journal, English - Changes in effective diffusivity for oxygen during neural activation and deactivation estimated from capillary diameter measured by two-photon laser microscope
Hiroshi Ito; Hiroyuki Takuwa; Yosuke Tajima; Hiroshi Kawaguchi; Takuya Urushihata; Junko Taniguchi; Yoko Ikoma; Chie Seki; Masanobu Ibaraki; Kazuto Masamoto; Iwao Kanno
JOURNAL OF PHYSIOLOGICAL SCIENCES, 67, 2, 325-330, Mar. 2017, Peer-reviwed
Scientific journal, English - Dynamic diameter response of intraparenchymal penetrating arteries during cortical spreading depression and elimination of vasoreactivity to hypercapnia in anesthetized mice
Miyuki Unekawa; Yutaka Tomita; Kazuto Masamoto; Haruki Toriumi; Takashi Osada; Iwao Kanno; Norihiro Suzuki
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 37, 2, 657-670, Feb. 2017, Peer-reviwed
Scientific journal, English - Long-term repeated in vivo real-time analysis of microglia in the mouse cortex with a closed-cranial window by Tomita-Seylaz method
Hiroya Yuki; Kazuto Masamoto; Miyuki Unekawa; Yutaka Tomita; Iwao Kanno; Norihiro Suzuki
Corresponding, Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism), The Japanese Society of Cerebral Blood Flow and Metabolism, 28, 2, 249-256, 2017, Peer-reviwed
Scientific journal - Dynamic Flow Velocity Mapping from Fluorescent Dye Transit Times in the Brain Surface Microcirculation of Anesthetized Rats and Mice
Ryo Hoshikawa; Hiroshi Kawaguchi; Hiroyuki Takuwa; Yoko Ikoma; Yutaka Tomita; Miyuki Unekawa; Norihiro Suzuki; Iwao Kanno; Kazuto Masamoto
Last, MICROCIRCULATION, 23, 6, 416-425, Aug. 2016, Peer-reviwed
Scientific journal, English - ASTROCYTIC DEPOLARIZATION INDUCED RAPID AND BROAD INCREASE IN CBF IN IN VIVO MOUSE CORTEX
K. Masamoto; M. Unekawa; T. Watanabe; H. Toriumi; H. Takuwa; H. Kawaguchi; I. Kanno; K. Matsui; K. Tanaka; Y. Tomita; N. Suzuki
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 36, 28-29, Jun. 2016
Scientific journal, English - BEHAVIOR OF RED BLOOD CELLS IN INTRAPARENCHYMAL CAPILLARIES DURING CORTICAL SPREADING DEPRESSION OBSERVED WITH HIGH-SPEED CAMERA CONFOCAL FLUORESCENCE MICROSCOPE IN ANESTHETIZED MICE
Y. Tomita; M. Unekawa; H. Toriumi; T. Osada; K. Masamoto; H. Kawaguchi; Y. Itoh; I. Kanno; N. Suzuki
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 36, 544-545, Jun. 2016
Scientific journal, English - Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model
Asuka Nishino; Yosuke Tajima; Hiroyuki Takuwa; Kazuto Masamoto; Junko Taniguchi; Hidekatsu Wakizaka; Daisuke Kokuryo; Takuya Urushihata; Ichio Aoki; Iwao Kanno; Yutaka Tomita; Norihiro Suzuki; Yoko Ikoma; Hiroshi Ito
SCIENTIFIC REPORTS, 6, 25072, Apr. 2016, Peer-reviwed
Scientific journal, English - Establishment and evaluation of a new highly metastatic tumor cell line 5a-D-Luc-ZsGreen expressing both luciferase and green fluorescent protein
Hitomi Sudo; Atsushi B. Tsuji; Aya Sugyo; Hiroyuki Takuwa; Kazuto Masamoto; Yutaka Tomita; Norihiro Suzuki; Takeshi Imamura; Mitsuru Koizumi; Tsuneo Saga
INTERNATIONAL JOURNAL OF ONCOLOGY, 48, 2, 525-532, Feb. 2016, Peer-reviwed
Scientific journal, English - Fluorescence Imaging of Blood Flow Velocity in the Rodent Brain
Kazuto Masamoto; Ryo Hoshikawa; Hiroshi Kawaguchi
Lead, CURRENT TOPICS IN MEDICINAL CHEMISTRY, 16, 24, 2677-2684, 2016, Peer-reviwed
Scientific journal, English - Unveiling astrocytic control of cerebral blood flow with optogenetics
Kazuto Masamoto; Miyuki Unekawa; Tatsushi Watanabe; Haruki Toriumi; Hiroyuki Takuwa; Hiroshi Kawaguchi; Iwao Kanno; Ko Matsui; Kenji F. Tanaka; Yutaka Tomita; Norihiro Suzuki
Lead, SCIENTIFIC REPORTS, 5, 11455, Jun. 2015, Peer-reviwed
Scientific journal, English - Hyperperfusion counteracted by transient rapid vasoconstriction followed by long-lasting oligemia induced by cortical spreading depression in anesthetized mice
Miyuki Unekawa; Yutaka Tomita; Haruki Toriumi; Takashi Osada; Kazuto Masamoto; Hiroshi Kawaguchi; Yoshiaki Itoh; Iwao Kanno; Norihiro Suzuki
Journal of Cerebral Blood Flow and Metabolism, Nature Publishing Group, 35, 4, 689-698, 31 Mar. 2015, Peer-reviwed
Scientific journal, English - Pial arteries respond earlier than penetrating arterioles to neural activation in the somatosensory cortex in awake mice exposed to chronic hypoxia: an additional mechanism to proximal integration signaling?
Yuta Sekiguchi; Hiroyuki Takuwa; Hiroshi Kawaguchi; Takahiro Kikuchi; Eiji Okada; Iwao Kanno; Hiroshi Ito; Yutaka Tomita; Yoshiaki Itoh; Norihiro Suzuki; Ryo Sudo; Kazuo Tanishita; Kazuto Masamoto
Last, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 34, 11, 1761-1770, Nov. 2014, Peer-reviwed
Scientific journal, English - Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy
Yosuke Tajima; Hiroyuki Takuwa; Daisuke Kokuryo; Hiroshi Kawaguchi; Chie Seki; Kazuto Masamoto; Yoko Ikoma; Junko Taniguchi; Ichio Aoki; Yutaka Tomita; Norihiro Suzuki; Iwao Kanno; Naokatsu Saeki; Hiroshi Ito
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 34, 8, 1363-1372, Aug. 2014, Peer-reviwed
Scientific journal, English - Cerebral hemodynamic response to acute hyperoxia in awake mice
Yosuke Tajima; Hiroyuki Takuwa; Asuka Nishino; Tetsuya Matsuura; Hiroshi Kawaguchi; Yoko Ikoma; Junko Taniguchi; Chie Seki; Kazuto Masamoto; Iwao Kanno; Naokatsu Saeki; Hiroshi Ito
BRAIN RESEARCH, 1557, 155-163, Apr. 2014, Peer-reviwed
Scientific journal, English - Vessel Specific Imaging of Glucose Transfer with Fluorescent Glucose Analogue in Anesthetized Mouse Cortex
Rei Murata; Yuki Takada; Hiroyuki Takuwa; Hiroshi Kawaguchi; Hiroshi Ito; Iwao Kanno; Naotomo Tottori; Yukio Yamada; Yutaka Tomita; Yoshiaki Itoh; Norihiro Suzuki; Katsuya Yamada; Kazuto Masamoto
Last, Advances in Experimental Medicine and Biology, Springer New York, 241-246, 22 Mar. 2014, Peer-reviwed
In book, English - Automated Image Analysis for Diameters and Branching Points of Cerebral Penetrating Arteries and Veins Captured with Two-Photon Microscopy
Takuma Sugashi; Kouichi Yoshihara; Hiroshi Kawaguchi; Hiroyuki Takuwa; Hiroshi Ito; Iwao Kanno; Yukio Yamada; Kazuto Masamoto
Last, Advances in Experimental Medicine and Biology, 209-215, 22 Mar. 2014, Peer-reviwed
In book, English - Microvascular sprouting, extension, and creation of new capillary connections with adaptation of the neighboring astrocytes in adult mouse cortex under chronic hypoxia
Kazuto Masamoto; Hiroyuki Takuwa; Chie Seki; Junko Taniguchi; Yoshiaki Itoh; Yutaka Tomita; Haruki Toriumi; Miyuki Unekawa; Hiroshi Kawaguchi; Hiroshi Ito; Norihiro Suzuki; Iwao Kanno
Lead, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 34, 2, 325-331, Feb. 2014, Peer-reviwed
Scientific journal, English - Reproducibility of measuring cerebral blood flow by laser-Doppler flowmetry in mice
Tajima Y; Takuwa H; Kawaguchi H; Masamoto K; Ikoma Y; Seki C; Taniguchi J; Kanno I; Saeki N; Ito H
Frontiers in Bioscience, IMR Press, E6, 1, 62-68, 2014, Peer-reviwed
Scientific journal, English - Hemodynamic changes during neural deactivation in awake mice: A measurement by laser-Doppler flowmetry in crossed cerebellar diaschisis
Hiroyuki Takuwa; Yosuke Tajima; Daisuke Kokuryo; Tetsuya Matsuura; Hiroshi Kawaguchi; Kazuto Masamoto; Junko Taniguchi; Yoko Ikoma; Chie Seki; Ichio Aoki; Yutaka Tomita; Norihiro Suzuki; Iwao Kanno; Hiroshi Ito
Brain Research, Elsevier BV, 1537, 350-355, Nov. 2013, Peer-reviwed
Scientific journal, English - Imaging of Tau Pathology in a Tauopathy Mouse Model and in Alzheimer Patients Compared to Normal Controls
Masahiro Maruyama; Hitoshi Shimada; Tetsuya Suhara; Hitoshi Shinotoh; Bin Ji; Jun Maeda; Ming-Rong Zhang; John Q. Trojanowski; Virginia M. -Y. Lee; Maiko Ono; Kazuto Masamoto; Harumasa Takano; Naruhiko Sahara; Nobuhisa Iwata; Nobuyuki Okamura; Shozo Furumoto; Yukitsuka Kudo; Qing Chang; Takaomi C. Saido; Akihiko Takashima; Jada Lewis; Ming-Kuei Jang; Ichio Aoki; Hiroshi Ito; Makoto Higuchi
NEURON, 79, 6, 1094-1108, Sep. 2013, Peer-reviwed
Scientific journal, English - Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex
Harumi Hotta; Kazuto Masamoto; Sae Uchida; Yuta Sekiguchi; Hiroyuki Takuwa; Hiroshi Kawaguchi; Kazuhiro Shigemoto; Ryo Sudo; Kazuo Tanishita; Hiroshi Ito; Iwao Kanno
Journal of Cerebral Blood Flow and Metabolism, 33, 9, 1440-1447, Sep. 2013, Peer-reviwed
Scientific journal, English - Hypoxia-Induced Cerebral Angiogenesis in Mouse Cortex with Two-Photon Microscopy
Kazuto Masamoto; Hiroyuki Takuwa; Yutaka Tomita; Haruki Toriumi; Miyuki Unekawa; Junko Taniguchi; Hiroshi Kawaguchi; Yoshiaki Itoh; Norihiro Suzuki; Hiroshi Ito; Iwao Kanno
Lead, Oxygen Transport to Tissue XXXV, 15-20, 04 Jun. 2013, Peer-reviwed
In book, English - Measuring the Vascular Diameter of Brain Surface and Parenchymal Arteries in Awake Mouse
Yuta Sekiguchi; Kazuto Masamoto; Hiroyuki Takuwa; Hiroshi Kawaguchi; Iwao Kanno; Hiroshi Ito; Yutaka Tomita; Yoshiaki Itoh; Norihiro Suzuki; Ryo Sudo; Kazuo Tanishita
Corresponding, Oxygen Transport to Tissue XXXV, Springer New York, 419-425, 04 Jun. 2013, Peer-reviwed
In book, English - Long-term adaptation of cerebral hemodynamic response to somatosensory stimulation during chronic hypoxia in awake mice
Hiroyuki Takuwa; Kazuto Masamoto; Kyoko Yamazaki; Hiroshi Kawaguchi; Yoko Ikoma; Yousuke Tajima; Takayuki Obata; Yutaka Tomita; Norihiro Suzuki; Iwao Kanno; Hiroshi Ito
Journal of Cerebral Blood Flow and Metabolism, 33, 5, 774-779, May 2013, Peer-reviwed
Scientific journal, English - Phantom and mouse experiments of time-domain fluorescence tomography using total light approach
Shinpei Okawa; Akira Yano; Kazuki Uchida; Yohei Mitsui; Masaki Yoshida; Masashi Takekoshi; Andhi Marjono; Feng Gao; Yoko Hoshi; Ikuhiro Kida; Kazuto Masamoto; Yukio Yamada
BIOMEDICAL OPTICS EXPRESS, 4, 4, 635-651, Apr. 2013, Peer-reviwed
Scientific journal, English - Potassium-induced cortical spreading depression bilaterally suppresses the electroencephalogram but only ipsilaterally affects red blood cell velocity in intraparenchymal capillaries
Miyuki Unekawa; Yutaka Tomita; Haruki Toriumi; Kazuto Masamoto; Iwao Kanno; Norihiro Suzuki
JOURNAL OF NEUROSCIENCE RESEARCH, 91, 4, 578-584, Apr. 2013, Peer-reviwed
Scientific journal, English - Three-dimensional cortex model including vascular structure for estimation of path length for optical imaging
Takahiro Kikuchi; Hiroyuki Takuwa; Kazuto Masamoto; Hiroshi Ito; Eiji Okada
Optics InfoBase Conference Papers, Optical Society of America, 2013
International conference proceedings, English - Image-based vessel-by-vessel analysis for red blood cell and plasma dynamics with automatic segmentation
Hiroshi Kawaguchi; Kazuto Masamoto; Hiroshi Ito; Iwao Kanno
Microvascular Research, 84, 2, 178-187, Sep. 2012, Peer-reviwed
Scientific journal, English - Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model
Y-N Jin; M. Inubushi; K. Masamoto; K. Odaka; I. Aoki; A. B. Tsuji; M. Sagara; M. Koizumi; T. Saga
GENE THERAPY, 19, 8, 836-843, Aug. 2012, Peer-reviwed
Scientific journal, English - Anesthesia and the quantitative evaluation of neurovascular coupling
Kazuto Masamoto; Iwao Kanno
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 32, 7, 1233-1247, Jul. 2012, Peer-reviwed
English - Repeated Longitudinal in Vivo Imaging of Neuro-glio-vascular Unit at the Peripheral Boundary of Ischemia in Mouse Cerebral Cortex
K. Masamoto; Y. Tomita; H. Toriumi; I. Aoki; M. Unekawa; H. Takuwa; Y. Itoh; N. Suzuki; I. Kanno
Neuroscience, 212, 190-200, 14 Jun. 2012
Scientific journal, English - Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice
Kazunori Miyazaki; Kazuto Masamoto; Nobutoshi Morimoto; Tomoko Kurata; Takahumi Mimoto; Takayuki Obata; Iwao Kanno; Koji Abe
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 32, 3, 456-467, Mar. 2012, Peer-reviwed
Scientific journal, English - Spatial Frequency-Based Analysis of Mean Red Blood Cell Speed in Single Microvessels: Investigation of Microvascular Perfusion in Rat Cerebral Cortex
Joonas Autio; Hiroshi Kawaguchi; Shigeyoshi Saito; Ichio Aoki; Takayuki Obata; Kazuto Masamoto; Iwao Kanno
PLOS ONE, 6, 8, e24056, Aug. 2011, Peer-reviwed
Scientific journal, English - Comparison of Temporal Response to Cerebral Blood Flow Measured by Laser Speckle Flowgraphy and Laser Doppler Flowmetry
Masashi Kusano; Haruka Nakayama; Hiroyuki Takuwa; Kazuto Masamoto; Iwao Kanno; Eiji Okada
Optics InfoBase Conference Papers, Optical Society of America (OSA), 2011
International conference proceedings, English - Reproducibility and variance of a stimulation-induced hemodynamic response in barrel cortex of awake behaving mice
Hiroyuki Takuwa; Joonas Autio; Haruka Nakayama; Tetsuya Matsuura; Takayuki Obata; Eiji Okada; Kazuto Masamoto; Iwao Kanno
Corresponding, BRAIN RESEARCH, 1369, 103-111, Jan. 2011, Peer-reviwed
Scientific journal, English - Frequency-dependent neural activity, CBF, and BOLD fMRI to somatosensory stimuli in isoflurane-anesthetized rats
Tae Kim; Kazuto Masamoto; Mitsuhiro Fukuda; Alberto Vazquez; Seong-Gi Kim
NEUROIMAGE, 52, 1, 224-233, Aug. 2010, Peer-reviwed
Scientific journal, English - Cerebrovascular dynamics in response to neural stimulation
Kazuto Masamoto; Takayuki Obata; Iwao Kanno
Hirosaki Medical Journal, 61, SUPPL., S181-S186, 08 Jul. 2010, Peer-reviwed
International conference proceedings, English - Changes in cerebral arterial, tissue and venous oxygenation with evoked neural stimulation: implications for hemoglobin-based functional neuroimaging
Alberto L. Vazquez; Mitsuhiro Fukuda; Michelle L. Tasker; Kazuto Masamoto; Seong-Gi Kim
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 30, 2, 428-439, Feb. 2010, Peer-reviwed
Scientific journal, English - Cerebral oxygen delivery and consumption during evoked neural activity
Vazquez AL; Masamoto K; Fukuda M; Kim SG
Frontiers in Neuroenergetics, Frontiers Media SA, 2, 11, 2010, Peer-reviwed
Scientific journal, English - Neurovascular coupling in primary auditory cortex investigated with voltage-sensitive dye imaging and laser-Doppler flowmetry
Hiroshi Kameyama; Kazuto Masamoto; Yoichi Imaizumi; Tetsuro Omura; Takusige Katura; Atsushi Maki; Kazuo Tanishita
Corresponding, Brain Research, 1244, 82-88, Dec. 2008, Peer-reviwed
Scientific journal, English - Dynamics of oxygen delivery and consumption during stimulation using a compartment model and CBF and tissue P-O2 measurements
Alberto L. Vazquez; Kazuto Masamoto; Seong-Gi Kim
NEUROIMAGE, 42, 1, 49-59, Aug. 2008, Peer-reviwed
Scientific journal, English - Multimodal Silica-Shelled Quantum Dots: Direct Intracellular Delivery, Photosensitization, Toxic, and Microcirculation Effects
Rumiana Bakalova; Zhivko Zhelev; Ichio Aoki; Kazuto Masamoto; Milka Mileva; Takayuki Obata; Makoto Higuchi; Veselina Gadjeva; Iwao Kanno
Bioconjugate Chemistry, American Chemical Society (ACS), 19, 6, 1135-1142, 22 May 2008, Peer-reviwed
Scientific journal, English - Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses
Kazuto Masamoto; Alberto Vazquez; Ping Wang; Seong-Gi Kim
Lead, NEUROIMAGE, 40, 2, 442-450, Apr. 2008, Peer-reviwed
Scientific journal, English - Imaging brain vasculature with BOLD microscopy: MR detection limits determined by in vivo two-photon microscopy
Sung-Hong Park; Kazuto Masamoto; Kristy Hendrich; Twao Kanno; Seong-Gi Kim
MAGNETIC RESONANCE IN MEDICINE, 59, 4, 855-865, Apr. 2008, Peer-reviwed
Scientific journal, English - Apparent diffusion time of oxygen from blood to tissue in rat cerebral cortex: implication for tissue oxygen dynamics during brain functions
Kazuto Masamoto; Jeff Kershaw; Masakatsu Ureshi; Naosada Takizawa; Hirosuke Kobayashi; Kazuo Tanishita; Iwao Kanno
Lead, Journal of Applied Physiology, 103, 4, 1352-1358, Oct. 2007, Peer-reviwed
Scientific journal, English - Arterial versus Total Blood Volume Changes during Neural Activity-Induced Cerebral Blood Flow Change: Implication for BOLD fMRI
Tae Kim; Kristy S Hendrich; Kazuto Masamoto; Seong-Gi Kim
Journal of Cerebral Blood Flow & Metabolism, 27, 6, 1235-1247, 20 Dec. 2006, Peer-reviwed
Scientific journal, English - Successive depth variations in microvascular distribution of rat somatosensory cortex
K Masamoto; T Kurachi; N Takizawa; H Kobayashi; K Tanishita
Lead, BRAIN RESEARCH, 995, 1, 66-75, Jan. 2004, Peer-reviwed
Scientific journal, English - Biphasic Changes in Tissue Partial Pressure of Oxygen Closely Related to Localized Neural Activity in Guinea Pig Auditory Cortex
Kazuto Masamoto; Tetsuro Omura; Naosada Takizawa; Hirosuke Kobayashi; Takusige Katura; Atsushi Maki; Hideo Kawaguchi; Kazuo Tanishita
Lead, Journal of Cerebral Blood Flow & Metabolism, 23, 9, 1075-1084, Sep. 2003, Peer-reviwed
Scientific journal, English - Dual responses of tissue partial pressure of oxygen after functional stimulation in rat somatosensory cortex
Kazuto Masamoto; Naosada Takizawa; Hirosuke Kobayashi; Kotaro Oka; Kazuo Tanishita
Lead, Brain Research, 979, 1-2, 104-113, Jul. 2003, Peer-reviwed
Scientific journal, English
MISC
- in vivoマウス大脳微小血管の４Dイメージング
正本和人; 須貸拓馬; 畝川美悠紀; 冨田裕; 菅野巖
メディカ出版, 10 Jun. 2019, 脳神経外科速報, 29, 6, 622-628, Japanese, Introduction commerce magazine - 光イメージングによる脳卒中の研究
正本和人
(株)中外医学社, 01 Aug. 2018, Clinical Neuroscience, 36, 8, 963-966, Japanese, Introduction commerce magazine - アストロサイトによる脳血流調節
正本和人; 畝川美悠紀; 冨田裕; 菅野巖; 鈴木則宏
先端医学社, Jan. 2016, 分子精神医学, 16, 1, 17-24, Japanese, Introduction commerce magazine, 1345-9082, 40020718101, AA11500190 - In vivo optical imaging of structural and functional plasticity of neurovascular unit
Kazuto Masamoto; Iwao Kanno
Lead, The Japanese Society of Cerebral Blood Flow and Metabolism, 2015, Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism), 26, 2, 99-105, Invited, 0915-9401, 2188-7519 - 光遺伝学による脳血流の操作
正本和人; 畝川美悠紀; 渡辺竜志; 結城浩弥; 田桑弘之; 川口拓之; 菅野巖; 松井広; 田中謙二; 冨田裕; 鈴木則宏
Lead, 07 Nov. 2014, レーザー学会研究会報告, 467th, 43-47, Japanese, 201402287202175286 - 脳表血管・細胞光イメージング
正本和人; 菅野巖
先端医学社, Jul. 2014, 分子脳血管病, 13, 2, 18-23, Japanese, Introduction commerce magazine - Hypoxia-induced adaptation of cerebral microvasculature.
Kazuto Masamoto; Hiroyuki Takuwa; Hiroshi Ito; Iwao Kanno
Feb. 2014, Microvascular Reviews and Communications, 6, 1, 13-18, English - ニューロサイエンスの最新情報 二光子顕微鏡法による脳の微小循環の測定・観察
正本和人; 菅野巖
(株)中外医学社, Nov. 2013, Clinical Neuroscience, 13, 11, 1340-1341, Japanese, Introduction commerce magazine, 0289-0585 - 前脳基底部の刺激で誘発される大脳皮質の層特異的な血管拡張反応
堀田晴美; 内田さえ; 正本和人; 菅野巖
31 Aug. 2013, 日本脳循環代謝学会機関誌, 24, supplement, 95-101, Japanese, Peer-reviwed, Invited, Introduction other - 脳賦活および脳機能抑制による局所脳有効酸素拡散能の変化ー毛細血管径の変化からの推定ー
伊藤浩; 田桑弘之; 川口拓之; 正本和人; 田島洋佑; 茨木正信; 菅野巖
31 Jul. 2013, 日本脳循環代謝学会機関誌, 24, 2, 25-28, Japanese, Peer-reviwed - マイネルト核刺激による大脳皮質層特異的な動脈拡張反応
堀田晴美; 正本和人; 内田さえ; 関口優太; 田桑弘之; 川口拓之; 重本和宏; 須藤亮; 谷下一夫; 伊藤浩; 菅野巌
12 May 2013, 基礎老化研究, 37, 2, 39, Japanese, 0912-8921, 201302201156077119 - Microscopic Optical Imaging of Neurovascular Coupling
MASAMOTO K.; KANNO I.
07 Dec. 2012, レーザー学会研究会報告 = Reports on the Topical meeting of the Laser Society of Japan, 437, (1)-(5), Japanese, 10031140326, AA11604414 - 脳虚血・低酸素モデルマウスにおける血管新生ライブイメージング
正本和人; 冨田裕; 鳥海春樹; 畝川美悠紀; 田桑弘之; 谷口順子; 川口拓之; 伊藤義彰; 鈴木則宏; 伊藤浩; 菅野巖
Sep. 2012, 日本脳循環代謝学会機関誌, 23, 2, 84-89, Japanese, Peer-reviwed, Invited - In Vivo imaging of neurovascular coupling with two-photon excitation laser scanning microscopy
Kazuto Masamoto; Iwao Kanno
社団法人 レーザー学会, Apr. 2012, The Review of Laser Engineering, 40, 4, 230-235, Japanese, Peer-reviwed, Invited, 0387-0200 - 脳機能賦活に起因するマウス皮質組織血流のレーザー計測
草野将史; 中山遙; 正本和人; 菅野巖; 岡田英史
一般社団法人 レーザー学会, Apr. 2012, The Review of Laser Engineering, 40, 4, 274-279, Japanese, Peer-reviwed, 0387-0200 - 脳微小血管と４Ｄイメージング
正本和人; 冨田裕; 菅野巖
メディカルレビュー社, 2012, Vascular Biology and Medicine, 13, 2, 53-60, Japanese, Introduction commerce magazine - 生物発光・蛍光と生体イメージング
山田幸生; 大川晋平; 正本和人
日本伝熱学会, 2011, 伝熱, 50, 210, 25-30, Japanese, Introduction other, 1344-8692, 10027724559, AA11315621 - 生体二光子顕微鏡による脳内微小循環径路の三次元追跡
正本和人; 川口拓之; 菅野巖
2011, 基礎老化研究, 35, 1, 25-28, Japanese, Introduction scientific journal - 光で探る神経血管カップリング
正本和人; 川口拓之; 田桑弘之; 山崎享子; 小畠隆行; 菅野巖
2010, 生体イメージングの未来, 230, 10-13, Japanese, Introduction other - Neurovascular coupling and its molecular mechanism
正本和人; 小畠隆行; 菅野巖
電気学会, 08 Feb. 2008, 光・量子デバイス研究会資料, OQD08, 1, 33-38, Japanese, 10025660720, AN00140211 - Oxygen transport in the microvessel network
K Tanishita; K Masamoto; T Negishi; N Takizawa; H Kobayashi
2005, ORGAN MICROCIRCULATION: A GATEWAY TO DIAGNOSITC AND THERAPEUTIC INTERVENTIONS, 13, 13-20, English, Peer-reviwed, WOS:000226302200002
Books and other publications
- 最新臨床脳卒中学（第２版）下ー最新の診断と治療ー
正本和人; 菅野
Textbook, Japanese, Contributor, XXVI.基礎研究の動向 脳微小循環制御, 日本臨牀社, 28 Feb. 2022 - 実験医学増刊 脳の半分を占めるグリア細胞 脳と心と体をつなぐ”膠”
正本和人
Scholarly book, Japanese, Contributor, 第２章 グリア細胞と神経免疫・臓器連関 グリアの光刺激による脳血流の操作, 羊土社, 01 Nov. 2019, 9784758103824 - 血流改善成分の開発と応用
Scholarly book, Japanese, Contributor, 第３章 血流障害と脳機能, シーエムシー出版, 30 Jul. 2018, 9784781313412 - 脳卒中病態学のススメ
Textbook, Japanese, Contributor, 9章 急性期脳梗塞モデル 4. 評価の方法（顕微鏡画像）, 南山堂, Feb. 2018 - Vascular remodeling after cerebral ischemia. (In: Primer on Cerebrovascular Diseases, Second Edition)
Nishijima Y; Akamatsu Y; Masamoto K; Liu J
Scholarly book, English, Joint work, Chapter 19, San Diego: Academic Press, 18 Mar. 2017 - New Horizons in Neurovascular Coupling : A Bridge between Brain Circulation and Neural Plasticity
Masamoto, Kazuto; Hirase, Hajime; Yamada, Katsuya
Scholarly book, English, Joint editor, Elsevier Science Serials, Apr. 2016 - Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow: Toward finding the determinants in maintaining the CBF homeostasis
I. Kanno; K. Masamoto
English, 2016 - ユニーク&エキサイティングサイエンスIII (総合コミュニケーション科学シリーズ)
正本和人
Scholarly book, Japanese, Contributor, 「呼吸する脳」への招待ー脳の機能を支える血液の流れと物質交換, 近代科学社, 26 Nov. 2014, 9784764904729 - シミュレーション辞典
日本シミュレーション学会
Dictionary or encycropedia, Japanese, Contributor, 分野：生命・医療・福祉 部門：医療「V-4］神経-血管相互作用, コロナ社, 27 Feb. 2012, 9784339024586 - からだと酸素の事典
酸素ダイナミクス研究会
Dictionary or encycropedia, Japanese, Contributor, 微小酸素電極の作製と測定の実際, 朝倉書店, 05 Sep. 2009, 9784254300987 - CBF and pO2 dynamics in rat cortex during neuronal activation by hind paw stimulation
K. Masamoto; J. Kershaw; M. Ureshi; N. Takizawa; H. Kobayashi; K. Tanishita; I. Kanno
English, Medpharm Scientific Publishers, 2004
Lectures, oral presentations, etc.
- 微小循環: 最も細い血管を見て知る体の健康
正本和人
Public discourse, Japanese, 2024年度矢上賞受賞記念講演, Invited
26 Oct. 2024 - Capillary flow imbalances under dehydration in the brain.
Kazuto Masamoto
Invited oral presentation, English, Joint Congress for the 3rd International Qi-Blood Conference and The 8th Chinese Microcirculation Week, Invited
07 Sep. 2024 - 脳における赤血球動態の解析
正本和人
Nominated symposium, Japanese, 日本機械学会 第 36回バイオエンジニアリング講演会 脳の循環と機能のバイオメカニクス（OS4-2）, Invited
11 May 2024 - 認知学習実験における温度環境の影響
井上幹太; 矢野祐希; 和田悠佑; 吉田智毅; 大下雅昭; 正本和人
Oral presentation, 第28回医用近赤外線分光法研究会・第26回酸素ダイナミクス研究会 合同研究会, 酸素ダイナミクス研究会, 鹿児島大学医学部 鶴陵会館（鹿児島）, https://kadaiqqicuhp.org/, Domestic conference
2022
01 Oct. 2022- 02 Oct. 2022
Research Themes
Media Coverage
- 脳の血流増加メカニズムの分離に成功
ニュースリリース 電気通信大学, 脳が活動すると活動部位の血液の流れが増えます。血液の流れを可視化することにより、脳のどこが活動したのかを計測することができます。従来、脳の活動によって生じる脳血管の反応については、ニューロンによる"直接の作用"と神経活動に付随して生じるグリア細胞の活動による"間接の作用"という、二つの経路によって脳の血流が増加することが分かっていました。しかし、二つの作用が独立に生じるのか、あるいは連結して生じるのかは不明でした。
脳血管の拡張機能が衰えると、認知症をはじめとした様々な脳の病気の発症につながるリスクが高まります。本成果によって、脳血管の機能の低下がニューロンの活動に由来するのか、あるいはグリア細胞の活動に由来するのかを病態に応じて明らかにすることが可能になり、将来的には原因となる細胞に特化した脳血管機能の回復、治療、機能低下の予防を行うことができると期待されます。
本研究は、慶應義塾大学医学部、東北大学大学院生命科学研究科、ならびに放射線医学総合研究所（現・量子医科学研究所）と共同で行いました。
15 Jun. 2021
