Kyushu University Academic Staff Educational and Research Activities Database
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Ataru Nishimura Last modified date:2020.07.02





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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/ataru-nishimura
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-5524
Fax
092-642-5526
Academic Degree
Ph.D.
Field of Specialization
cerebrovascular disease, molecular biology of cerebral aneurysm and brain ischemia
Outline Activities
Clinical research about surgical treatment and endovascular treatment of cerebrovascular disease, basic research about molecular biology of brain ischemia
Research
Research Interests
  • Role of Nox family proteins in formation of the cerebral aneurysm
    keyword : cerebral aneurysm, Nox family proteins
    2016.01~2017.03.
  • molecular biology of brain ischemia
    keyword : brain ischemia
    2015.04~2015.12.
Academic Activities
Papers
1. 西村 中, Detrimental role of pericyte Nox4 in the acute phase of brain ischemia, J Cereb Blood Flow Metab, 2015.10.
2. 西村 中, Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan ― J-ASPECT Study ―, Circ J, 2019.10.
Presentations
1. 西村 中, Periprocedual risk of treatment for carotid stenosis complicated with cardiac disease: J-ASPECT study, International Stroke Conference 2020, 2020.02.
2. 西村 中, Development of the Close The Gap-Stroke in the J-ASPECT Study: a nationwide quality improvement initiative of Japan, International Stroke Conference 2019, 2019.02.
3. 西村 中, Clinical outcomes of unruptured cerebral aneurysms treated with clipping or coiling in Japan: The J-ASPECT study, International Stroke Conference 2016, 2016.02.
4. Ataru Nishimura, Roles of pericyte NADPH oxidase 4 in acute brain ischemia, Neuroscience 2014, 2014.11, Pericytes, mural cells in capillary vessels, exist abundantly in the brain and compose the neurovascular unit with endothelial cells, glial cells, and neurons. It has been elucidated that pericytes play a key role in the formation and maintenance of the blood-brain barrier (BBB) because pericytes crucially affect the expression of proteins related to tight junction formed by endothelial cells and produce matrix metalloproteinases (MMPs) that regulate BBB stability. The NADPH oxidase family proteins are major reactive oxygen species (ROS)-producing enzymes. We have reported that Nox4 is abundantly expressed in pericytes. Our goal was to elucidate the roles of Nox4 in brain pericytes during acute brain ischemia.
We confirmed by quantitative PCR (qPCR) that Nox4 was expressed in human cultured brain microvascular pericytes (HBMPC) among the NADPH oxidase family and was significantly upregulated by hypoxia (at 1% O2 for 48 hours) by 7.8-fold (p < 0.05). We produced a mouse MCAO stroke model and examined the expression pattern of Nox4 in the brain. Immunofluorescent double labeling demonstrated that Nox4 expression was upregulated in microvessels particularly in peri-infarct areas and was co-stained with PDGFRβ, a pericyte marker. In order to elucidate the role of Nox4 in brain pericyte during brain ischemia, we generated mice with pericyte-specific human Nox4 overexpression using an SM22α promoter (Tg-Nox4). We confirmed that SM22α was expressed both in HBMPC by immunoblot and in mouse brain pericytes by co-immunostaining with PDGFRβ. We isolated microvessels from Tg-Nox4 brain and confirmed that human Nox4 mRNA was highly expressed in the vessels. We applied Tg-Nox4 to a MCAO model, and found that infarct volume was significantly larger in Tg-Nox4 than in littermate controls. Confocal laser scanning microscopy demonstrated that IgG leakage, an indicator of BBB breakdown, in peri-infarct areas was significantly increased in Tg-Nox4, suggesting that Nox4 overexpression in pericytes enhanced BBB breakdown during brain ischemia. To elucidate the mechanisms underlying the Nox4-mediated increased BBB breakdown, we induced adenoviral-mediated overexpression of Nox4 in HBMPC. We demonstrated that Nox4 overexpression increased NFκB phosphorylation and MMP9 expression in the cells. We also confirmed that NFκB phosphorylation and MMP9 activity was increased in Tg-Nox4 mouse.
In conclusion, Nox4 may be a major source of ROS in brain pericytes and is upregulated directly by hypoxia in peri-infarct areas during acute brain ischemia. Pericyte Nox4 may enhance BBB breakdown through the activation of NFκB-MMP9 signaling during acute brain ischemia.
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Educational
Educational Activities
Education about cerebrovascular disease
Other Educational Activities
  • 2015.04.