Strategy for hypoxic-ischemic encephalopathy in newborn infants to reduce oxygen free radicals by adjusting hydrogen and oxygen

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kagawa University
• Principal Investigator: KUSAKA Takashi 香川大学, 医学部附属病院, 講師 (50274288)
• Co-Investigator(Kenkyū-buntansha): UENO Masaki 香川大学, 医学部, 準教授 (30322267) ; MIKI Takanori 香川大学, 医学部, 準教授 (30274294) ; YASUDA Saneyuki 香川大学, 医学部附属病院, 助教 (00380155) ; IWASE Takashi 香川大学, 医学部附属病院, 助教 (30284368) ; NISHIDA Tomoko 香川大学, 教育学部, 教授 (00243759)
• Project Period (FY): 2010 – 2012
• Keywords: 低酸素性虚血性脳症 / 脳波 / 脳血液量 / 動物モデル / 虚血再還流 / 新生仔豚 / 低酸素虚血負荷 / 近赤外光

Research Abstract

In these studies, we found that combining the cerebral blood volume (CBV) with amplitude-integrated EEG (aEEG) is a more effective guide to control hypoxic/ischemic (HI) insult in a newborn piglet model than aEEG alone, to produce a consistent degree of survivable neuropathological damage. Next, we found that an early CBV increase and longer low-ampitude EEG after insult indicates severe brain injury. Finally, we revealed that Edaravone (a free radical scavenger) reduced histologic neuronal damage related to HI loading in our piglet HI model.

Research Products

• [Journal Article] CD36 expression in the brains of SAMP8 (2013)
  • Author(s): Wu B, Ueno M, Kusaka T, Miki T, Nagai Y, Nakagawa T, Kanenishi K, Hosomi N, Sakamoto H
  • Journal Title: Arch Gerontol Geriatr Volume: 56 Pages: 75-9
• [Journal Article] The relationship between muscle weakness and activation of the cerebral cortex early after unicompartmental knee arthroplasty (2013)
  • Author(s): Morita S, Kusaka T, Tanaka S, Yamada E, Arima N, Itoh S, Yamamoto T
  • Journal Title: J. Phys. Ther. Sci. Volume: 25(in press)
• [Journal Article] Temporal alteration of serum G-CSF and VEGF levels in perinatal asphyxia treated with head cooling (2012)
  • Author(s): Okazaki K, Kusaka T, Kondo M, Kozawa K, Yoshizumi M, Kimura H
  • Journal Title: Cytokine Volume: 60 Pages: 812-4
• [Journal Article] A developmental change of the visual behavior of the face recognition in the early infancy. (2012)
  • Author(s): Konishi Y, Okubo K, Kato I, Ijichi S, Nishida T, Kusaka T, Isobe K, Itoh S, Kato M, Konishi Y.
  • Journal Title: Brain Dev Volume: 34 Pages: 719-22
• [Journal Article] Cerebral blood volume combined with amplitude-integrated EEG can be a suitable guide to control hypoxic/ischemic insult in a piglet model. (2012)
  • Author(s): Nakamura S, Kusaka T, Yasuda S, Ueno M, Miki T, Koyano K, Nakamura M, Okada H, Okazaki K, Isobe K, Itoh S
  • Journal Title: Brain Dev
  • DOI: doi:10.1016/j.braindev.2012.10.007
• [Journal Article] The effect of blood transfusion on cerebral hemodynamics in preterm infants (2012)
  • Author(s): Koyano K, Kusaka T, Nakamura S, Nakamura M, Konishi Y, Miki T, Ueno M, Yasuda S, Okada H, Nishida T, Isobe K, Itoh S.
  • Journal Title: The effect of blood transfusion on cerebral hemodynamics in preterm infants
  • DOI: doi:10.1111/j.1537-2995.2012.03953.x
• [Journal Article] Cellular cholesterol levels in platelets before and after liver transplantation in a child with Alagille syndrome complicated by severe hypercholesterolemia. (2012)
  • Author(s): Ijichi S, Kusaka T, Okada H, Tada S, Isobe K, Itoh S
  • Journal Title: J Pediatr Gastroenterol Nutr
• [Journal Article] Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain (2012)
  • Author(s): Kato I, Kusaka T, Nishida T, Koyano K, Nakamura S, Nakamura M, Konishi Y, Kunikata J, Jinnai W, Yasuda S, Okada H, Itoh S, Isobe K
  • Journal Title: Brain Dev
• [Journal Article] 新生児領域における近赤光を利用した脳機能,循環代謝評価 (2012)
  • Author(s): 日下隆
  • Journal Title: NIRS-基礎と臨床- Pages: 198-204
• [Journal Article] 新生児蘇生の実際のポイント (2012)
  • Author(s): 日下隆
  • Journal Title: 香川産科婦人科雑誌 Volume: 14 Pages: 9-14
• [Journal Article] 小谷野耕佑.周産期医が習得したい専門手技-新生児編 (2012)
  • Author(s): 日下隆
  • Journal Title: 超音波 脳. 周産期医学 Volume: 42 Pages: 1653-6
• [Journal Article] Hemodynamic changes in the breast and frontal cortex of mothers during breastfeeding (2011)
  • Author(s): Tanimoto K, Kusaka T, Nishida T, Ogawa K, Kato I, Ijichi S, Mikami J, Sobue I, Isobe, K, Itoh S
  • Journal Title: Pediatr Res Volume: 70 Pages: 400-5
• [Journal Article] The expression of CD36 in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model. (2011)
  • Author(s): Ueno M, Nakagawa T, Nagai Y, Nishi N, Kusaka T, Kanenishi K, Onodera M, Hosomi N, Huang CL, Yokomise H, Tomimoto H, Sakamoto H.
  • Journal Title: Neuropathol Appl Neurobiol Volume: 37 Pages: 727-37
• [Journal Article] Functional lateralization of sensorimotor cortex in infants measured using multi-channel near-infrared spectroscopy (2011)
  • Author(s): Kusaka T, Isobe K, Miki T, Ueno M, Koyano K, Nakamura S, Nakamura M, Konishi Y, Kuboi T, Kato I, Okubo K, Yasuda S, Nishida T, Itoh S
  • Journal Title: Pediatr Res Volume: 69 Pages: 430-5
• [Journal Article] Reduction of image artifacts induced by change in the optode coupling in time-resolved diffuse optical tomography (2011)
  • Author(s): Fukuzawa R, Okawa S, Matsuhashi S, Kusaka T, Tanikawa Y, Hoshi Y, Gao F, Yamada Y.
  • Journal Title: J Biomed Opt Volume: 16 Pages: 116022
• [Journal Article] 新生児集中治療室での赤ちゃんの脳障害を防ぐための脳循環や代謝の評価. (2011)
  • Author(s): 日下隆
  • Journal Title: ベビーサイエンス Volume: 11 Pages: 2-7
• [Journal Article] Axonal damage in acute cerebral infarction showing ADC reduction (2010)
  • Author(s): Ueno M, Onodera M, Naya T, Toyama Y, Hosomi N, Huang CL, Nishiyama Y, Kusaka T, Miki Y, Kohno M, Tomimoto H, Sakamoto H
  • Journal Title: J Neurol Volume: 257 Pages: 1559-61
• [Journal Article] Short-term exposure to ethanol causes a differential response between nerve growth factor and brain-derived neurotrophic factor ligand/receptor systems in the mouse cerebellum (2010)
  • Author(s): Wang ZY, Miki T, Lee KY, Yokoyama T, Kusaka T, Sumitani K, Warita K, Matsumoto Y, Yakura T, Hosomi N, Ameno K, Bedi KS, Takeuchi Y
  • Journal Title: Neuroscience Volume: 165 Pages: 485-9
• [Journal Article] The expression of LDL receptor in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model. (2010)
  • Author(s): Ueno M, Wu B, Nakagawa T, Nagai Y, Onodera M, Huang CL, Kusaka T, Kanenishi K, Sakamoto H
  • Journal Title: Histochem Cell Biol Volume: 133 Pages: 669-76
• [Journal Article] 近赤外光を利用した新生児の脳循環・代謝評価 (2010)
  • Author(s): 日下隆
  • Journal Title: 臨床脳波 Volume: 52 Pages: 268-73
• [Presentation] 低酸素虚血後早期の脳血液量と脳波変化の関係について～新生仔豚仮死モデルによる基礎的研究～ (2012)
  • Author(s): 中村信嗣、神内済、國方淳、小谷野耕佑、中村信、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 日本周産期新生児学会学術集会
  • Place of Presentation: 埼玉県・大宮市
  • Year and Date: 20120700
• [Presentation] 新生児頭部における光学特性(吸光係数及び散乱係数)の血中ヘモグロビン濃度変化による影響について (2012)
  • Author(s): 小谷野耕佑、中村信嗣、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第19回医用近赤外線分光法研究会
  • Place of Presentation: 東京都
  • Year and Date: 2012-10-13
• [Presentation] The Impact of Blood Transfusion on Cerebral Hemodynamics and Oxygenation in Anemic Preterm Infants (2012)
  • Author(s): Koyano K, Jinnai W, Nakamura S, Nakamura M, Yasuda S, Kusaka T, Isobe K, Itoh S
  • Organizer: The 8th Congressof Asian Society for Pediatric Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-05-18
• [Presentation] Cerebral Blood Volume (CBV) Using Near-infrared Time-resolved Spectroscopy (TRS) and AEEG Evaluation after Hypoxic-ischemic Insult in Newborn piglets. (2012)
  • Author(s): Nakamura M, Nakamura S, Koyano K, Jinnai W, Yasuda S, Miki T, Ueno M, KusakaT, Isobe K, Itoh S
  • Organizer: The 8th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-05-18
• [Presentation] Early Changes in Cerebral Blood Volume after Asphyxia Impacts for Neuropathological Prognosis in Newborn Piglets (2012)
  • Author(s): Nakamura S, Jinnai W, Koyano K, UenoM, Miki T, Nakamura M, Yasuda S, Kusaka T, Isobe K, Itoh S.
  • Organizer: The 8th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-05-18
• [Presentation] Cerebral Perfusion Impairments during Asphyxia Impacts for Neuropathological Prognosis in Newborn Piglets. (2012)
  • Author(s): Jinnai W, Nakamura S, Koyano K,Ueno M, Miki T, Nakamura M, Yasuda S, Kusaka T, Isobe K, Itoh S.
  • Organizer: The 8th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-05-18
• [Presentation] 新生仔豚仮死モデルにおける低酸素虚血後の脳循環変化と脳波変化の関係について (2012)
  • Author(s): 中村信嗣、神内済、國方淳、小谷野耕佑、中村信、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 日本小児科学会学術集会
  • Place of Presentation: 福岡県・福岡市
  • Year and Date: 2012-04-22
• [Presentation] 新生仔豚仮死モデルでの低酸素負荷中の脳循環変化と低酸素負荷 5 日後の病理組織学的予後の関係 (2011)
  • Author(s): 中村信嗣、神内済、國方淳、小谷野耕佑、中村信、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第56回日本未熟児新生児学会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-13
• [Presentation] 未熟児貧血における輸血療法時の脳血液量、脳内ヘモグロビン酸素飽和度の変化について (2011)
  • Author(s): 小谷野耕佑、神内済、國方淳、中村信嗣、中村信、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第56回日本未熟児新生児学会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-13
• [Presentation] 新生仔豚仮死モデルによる低酸素負荷後早期の脳循環の検討(第2 報)-脳血液量と aEEG の関係 (2011)
  • Author(s): 中村信嗣、神内済、國方淳、小谷野耕佑、中村信、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第56回日本未熟児新生児学会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-13
• [Presentation] 新生仔豚低酸素虚血モデルにおける活性酸素スカベンジャーの蘇生後早期の脳循環に与える影響 (2011)
  • Author(s): 日下隆、中村信嗣、小谷野耕佑、中村信、神内済、國方淳、安田真之、磯部健一、伊藤進.
  • Organizer: 第38回日本小児臨床薬理学会
  • Place of Presentation: 滋賀県・大津市
  • Year and Date: 2011-11-03
• [Presentation] 近赤外線時間分解分光装置 (TRS) を用いて測定した未熟児貧血における輸血療法時の脳血液量、脳内ヘモグロビン酸素飽和度の変化について (2011)
  • Author(s): 小谷野耕佑、中村信嗣、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第18回医用近赤外線分光法研究会
  • Place of Presentation: 岐阜県・岐阜市
  • Year and Date: 2011-10-22
• [Presentation] 新生児における酸素毒性を回避するための脳循環・酸素代謝評価 (2011)
  • Author(s): 日下隆
  • Organizer: 第15回酸素ダイナミクス研究会
  • Place of Presentation: 佐賀県・佐賀市
  • Year and Date: 2011-09-10
• [Presentation] 新生仔豚を用いた遅発性脳エネルギー代謝障害時の脳循環と脳代謝の基礎的検討学 (2011)
  • Author(s): 安田真之、神内済、松岡剛司、中村信、小谷野耕佑、中村信、大久保賢介、日下隆、磯部健一、伊藤進
  • Organizer: 第114回日本小児科学会
  • Place of Presentation: 東京都
  • Year and Date: 2011-08-12
• [Presentation] 新生仔豚低酸素虚血モデルを用いた活性酸素スカベンジャーの蘇生後早期の脳循環に与える影響 (2011)
  • Author(s): 日下隆、 中村信嗣、小谷野耕佑、中村信、安田真之、磯部健一、伊藤進
  • Organizer: 第47回日本周産期・新生児医学会
  • Place of Presentation: 北海道・札幌市
  • Year and Date: 2011-07-10
• [Presentation] 新生仔豚仮死モデルを用いた遅発性脳エネルギー代謝障害時の脳循環と脳代謝の基礎的検討 (2011)
  • Author(s): 安田真之、 神内済、松岡剛司、中村信嗣、小谷野耕佑、中村信、大久保賢介、日下隆、磯部健一、伊藤進
  • Organizer: 第47回日本周産期・新生児医学会
  • Place of Presentation: 北海道・札幌市
  • Year and Date: 2011-07-10
• [Presentation] Cerebral blood volume is the most effective guide to control for the Hypoxic/Ischemic insult in a newborn piglet model (2011)
  • Author(s): Kusaka T, Nakamura S, Koyano K, Nakamura M, Yasuda S, Okubo K, Isobe K, Itoh S, Ueno M, Miki T
  • Organizer: BRAIN'11 & BRAINPET'11
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-05-25
• [Presentation] The impact of blood transfusionon cerebral hemodynamics and oxygenation in anemic preterm infants. (2011)
  • Author(s): Koyano K, Nakamura S, Koyano K, YasudaS, Okubo K, Nakamura M, Kusaka T, Isobe K, Itoh S.
  • Organizer: BRAIN'11 & BRAINPET'11
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-05-25
• [Presentation] Early (24 Hr) Measurement of the Increment Rate of Transcutaneous Biliruibin Is Useful in Predicting Severe Hyperbilirubinemia in Severe Hemolytic Disease (2011)
  • Author(s): Nakamura S, Yamamoto M, Kato I, KusakaT, Isobe K, Itoh S
  • Organizer: The 7th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-04-30
• [Presentation] Relationship between Cerebral Hemodynamics and Metabolism during Secondary Cerebral Energy Failure Using a Piglet Hypoxic-Ischemic Model (2011)
  • Author(s): Yasuda S, Nakamura M, Nakamura S, Koyano K, Okubo K, Kusaka T, Isobe K, Itoh S
  • Organizer: The 7th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-04-30
• [Presentation] Which Is the Most Effective Guide To Control Hypoxic/Ischemic Insult in a Newborn Piglet Model? Cerebral Electrocortical Activity Versus Cerebral Blood Volume (2011)
  • Author(s): Nakamura S, Koyano K, Ueno M, Miki T, Nakamura M, Ijichi S, Yasuda S, Okubo K, Kusaka T, Isobe K, Itoh S
  • Organizer: The 7th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-04-30
• [Presentation] Cerebral Blood Volume Evaluation Using Near-Infrared Time Resolved Spectroscopy after Hypoxic Ischemic Insult in Newborn Piglets. (2011)
  • Author(s): Nakamura M, Nakamura S, Koyano K, Matsuoka T, Yasuda S, Okubo K, Kusaka T, Isobe K, Itoh S, Miki T, Ueno M
  • Organizer: The 7th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-04-30
• [Presentation] Influence of a Free Radical Scavenger on Cerebral Circulation Early after Resuscitation in a Newborn Piglet Hypoxic-Ischemic Model (2011)
  • Author(s): Kusaka T, Nakamura S, Koyano K, UenoM, Miki T, Nakamura M, Yasuda S, Okubo K, Isobe K, Itoh S
  • Organizer: The 7th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-04-30
• [Presentation] 新生仔豚仮死モデルによる低酸素負荷後早期の脳循環の検討 (2010)
  • Author(s): 中村信、中村信嗣、小谷野耕佑、松岡剛司、安田真之、大久保賢介、日下隆、磯部健一、伊藤進
  • Organizer: 第55回日本未熟児新生児学会学術集会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2010-11-07
• [Presentation] 生仔豚を用いた長期予後検討可能な新生児仮死モデル作成の検討(第7 報):aEEG を指標とした負荷 vs 脳血液量を指標とした負荷 (2010)
  • Author(s): 中村信嗣、小谷野耕佑、加藤育子、松岡剛司、中村信、安田真之、大久保賢介、日下隆、磯部健一、伊藤進
  • Organizer: 第55回日本未熟児新生児学会学術集会
  • Place of Presentation: 兵庫県・神戸市
  • Year and Date: 2010-11-06
• [Presentation] 新生仔豚を用いた急性貧血モデルにおける脳循環の代償性変化 (2010)
  • Author(s): 小谷野耕佑、小谷野薫、伊地知園子、加藤育子、小西行彦、久保井徹、大久保賢介、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第46回日本周産期・新生児医学会学術集会
  • Place of Presentation: 兵庫県、神戸市
  • Year and Date: 2010-07-13
• [Presentation] 新生仔豚を用いた長期予後検討可能な新生児仮死モデルの検討(第5 報) (2010)
  • Author(s): 安田真之、大橋育子、中村信嗣、小谷野耕佑、久保井徹、大久保賢介、中村信、日下隆、今井正、磯部健一、伊藤進
  • Organizer: 第46回日本周産期・新生児医学会学術集会
  • Place of Presentation: 兵庫県、神戸市
  • Year and Date: 2010-07-13
• [Presentation] 新生仔豚を用いた長期予後検討可能な新生児仮死モデルの検討(第6 報):蘇生後の脳血液再潅流について (2010)
  • Author(s): 中村信嗣、小谷野耕佑、中村信、加藤育子、松岡剛司、大久保賢介、安田真之、日下隆、磯部健一、伊藤進
  • Organizer: 第46回日本周産期・新生児医学会学術集会
  • Place of Presentation: 兵庫県、神戸市
  • Year and Date: 2010-07-13
• [Presentation] 新生仔豚低酸素性虚血モデルでの脳波振幅と脳循環のミスマッチと予後との関係 (2010)
  • Author(s): 日下隆、安田真之、中村信嗣、小谷野耕佑、久保井徹、大久保賢介、西田智子、今井正、磯部健一、伊藤進
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 岩手県、盛岡市
  • Year and Date: 2010-04-23