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Faculty of Medicine College Hospital Mother and child health center of integrated perinatal period |
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AOKI Yoshinori
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Research Areas 【 display / non-display 】
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Life Science / Embryonic medicine and pediatrics
Papers 【 display / non-display 】
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Aoki Y., Dai H., Furuta F., Akamatsu T., Oshima T., Takahashi N., Goto Y.i., Oka A., Itoh M.
Cell Communication and Signaling 21 ( 1 ) 126 2023.6
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Cell Communication and Signaling
Background: Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 and the molecular mechanism of LOX-1 gene transcription microglial cells under hypoxic and ischemic conditions. Methods: We isolated primary rat microglial cells from 3-day-old rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positivity with immunocytochemistry. We treated primary rat microglial cells with oxygen glucose deprivation (OGD) as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines in cells treated with or without siRNA and inhibitors compared with those of cells that did not receive OGD-treatment. To confirm transcription factor binding to the OLR-1 gene promoter under the OGD conditions, we performed a luciferase reporter assay and chromatin immunoprecipitation assay. In addition, we analyzed reactive oxygen species and cell viability. Results: We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1β, IL-6 and TNF-α; the chemokines CCL2, CCL5 and CCL3; and reactive oxygen/nitrogen species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of inflammatory mediators. We found that NF-κB and HIF-1α bind to the promoter region of the OLR-1 gene. Based on the results of the luciferase reporter assay, NF-κB has strong transcriptional activity. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway. Conclusion: The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated the immune system. LOX-1 and its related molecules or chemicals may be major therapeutic candidates. [MediaObject not available: see fulltext.].
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Yoshinori Aoki, Tatsuo Kono, Mikako Enokizono, Kaoru Okazaki
BMC pediatrics 21 ( 1 ) 224 2021.5
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
Background: Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes.
Methods: We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children's Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge.
Results: In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1-3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome.
Conclusions: 18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy. -
Pulmonary lymphangiectasia in an extremely preterm infant complicated with <i>Ureaplasma</i> pneumonitis
Sakakibara Kouhei, Yamada Naoshi, Kodama Yuki, Obata Shizuka, Tsuzuki Yasue, Muraoka Junsuke, Aoki Yoshinori, Yamashita Rie, Nakame Kazuhiko, Kaneko Masatoki, Katsuragi Shinji, Tsuzuki Ryo, Sato Yuichiro
Journal of Japan Society of Perinatal and Neonatal Medicine 59 ( 1 ) 116 - 121 2023
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society of Perinatal and Neonatal Medicine
Here we report a case of pulmonary lymphangiectasia that caused exacerbation of respiratory status after an infection. A preterm infant born at 23 weeks of gestation without obvious clinical intrauterine infection showed worsening respiratory status and increased c-reactive protein on day 15 of life. Chest X-ray showed consolidation in right upper lobe and whole left lung. Several broad-spectrum antibiotics were administered unsuccessfully. Finally, <i>Ureaplasma urealyticum</i> was detected in sputum culture, and azithromycin was administered. Although the inflammation improved, tension pneumothorax and pulmonary hypertension developed and he died on day 44 of life. At autopsy, there were few findings of lung inflammation, and congenital lymphangiectasia was diagnosed. It seems that exacerbation was triggered by the infection, although there was no remarkable evidence to support causality. There have been few case reports of pulmonary lymphangiectasia in extremely low birth weight infants. This case was considered to be classified as primary, although the respiratory condition at birth was relatively good. There are no clear diagnostic criteria for this disease and no effective treatments. Clinically, neonatologists should keep in mind pulmonary lymphangiectasia if respiratory failure in newborns does not respond to common treatment approach.
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Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Related Microglial Activation in Neonatal Hypoxic-Ischemic Encephalopathy: Morphologic Consideration.
Akamatsu T, Sugiyama T, Oshima T, Aoki Y, Mizukami A, Goishi K, Shichino H, Kato N, Takahashi N, Goto YI, Oka A, Itoh M
The American journal of pathology 191 ( 7 ) 1303 - 1313 2021.7
Language：English Publishing type：Research paper (scientific journal)
Grant-in-Aid for Scientific Research 【 display / non-display 】
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低酸素性虚血性脳症におけるミクログリアでのLOX-1の役割解明と新規治療法の開発
Grant number：20K16875 2020.04 - 2023.03
独立行政法人日本学術振興会 科学研究費補助金 若手研究
Authorship：Principal investigator