The effect of hypothermia therapy on cortical laminar disruption following ischemic injury in neonatal mice

• Project/Area Number: 23791603
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Yamaguchi University
• Principal Investigator: KIDA Hiroyuki 山口大学, 大学院医学系研究科, 助教 (70432739)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 脳性麻痺 / 低酸素虚血 / 低体温療法 / 新生児

Research Abstract

Cerebral ischemia was induced in P3 mice with a right common carotid artery ligation followed by hypoxia (6% O2, 37 °C) for 30 min. Immediately after hypoxic ischemia, mice were exposed to hypothermia or normothermia for 24 h. The laminar structure of the cortex was examined with immunohistochemistry (Cux1/Ctip2); the number of neurons was counted; and the expression of myelin basic protein (MBP) was determined. The hypothermia treatment was associated with improved neurological outcomes in the behavioral test. In the normothermia group, histological analyses indicated reduced numbers of neurons, reduced cortical laminar thickness in the deep, ischemic cortical layers, and significant reduction in MBP expression in the ischemic cortex compared to the contralateral cortex. In the hypothermia group, no reductions were noted in deep cortical layer thickness and in MBP expression in the ischemic cortex compared to the contralateral cortex. Our findings may provide a basis for testing hypothermal therapies in patients with cerebral palsy induced by hypoxic ischemia in the preterm period.

Research Products

• [Journal Article] The effect of hypothermia therapy on cortical laminar disruption following ischemic injury in neonatal mice (2013)
  • Author(s): Kida H, Nomura S, Shinoyama M, Ideguchi M, Owada Y and Suzuki M
  • Journal Title: PLOS ONE Volume: (In press)
  • Peer Reviewed
• [Journal Article] Penicillin-induced epileptiform activity elevates focal brain temperature in anesthetized rats. (2013)
  • Author(s): Tokiwa T, Inoue T, Fujii M, Ishizuka S, Aou S, Kida H, Maruta Y, Yamakawa T, Nomura S, Suzuki M, Yamakawa T.
  • Journal Title: Neurosci Res. Volume: 76 Issue: 4 Pages: 257-260
  • DOI: 10.1016/j.neures.2013.05.001
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: analysis from a neurophysiological perspective. (2013)
  • Author(s): Yeting He
  • Journal Title: Brain Res Volume: 1497 Pages: 53-60
  • DOI: 10.1016/j.brainres.2012.11.041
  • Peer Reviewed
• [Journal Article] Penicillin-induced epileptiform activity elevates focal brain temperature in anesthetized rats (2013)
  • Author(s): Tokiwa T
  • Journal Title: Neuroscience Research Volume: in press
  • Peer Reviewed
• [Journal Article] The effect of hypothermia therapy on cortical laminar disruption following ischemic injury in neonatal mice (2013)
  • Author(s): Kida H
  • Journal Title: PLOS ONE Volume: in press
  • Peer Reviewed
• [Journal Article] Focal brain cooling terminates the faster frequency components of epileptic discharges induced by penicillin G in anesthetized rats. (2012)
  • Author(s): Hiroyuki Kida
  • Journal Title: Clin Neurophysiol Volume: 123 Issue: 9 Pages: 1708-1713
  • DOI: 10.1016/j.clinph.2012.02.074
  • Peer Reviewed
• [Journal Article] Effects of intrathecal baclofen therapy on motor and cognitive functions in a rat model of cerebral palsy (2012)
  • Author(s): Nomura S, Kagawa Y, Kida H, Maruta Y, Imoto H, Fujii M, Suzuki M
  • Journal Title: J Neurosurg Pediatr Volume: 9(2) Issue: 2 Pages: 209-15
  • DOI: 10.3171/2011.10.peds11209
  • Peer Reviewed
• [Journal Article] The effect of focal brain cooling on epileptic discharges in rats: Frequency analysis of electroencephalography (2011)
  • Author(s): Hiroyuki Kida, Masami Fujii, Takao Inoue, Yeting He, Yuichi Maruta, Sadahiro Nomura, Kazuhiro Taniguchi, Takuya Ichikawa, Takashi Saito, Michiyasu Suzuki
  • Journal Title: The 2011 IEEE International Conference on Systems, Man, and Cybernetics Volume: SMC 2011 Pages: 686-690
  • Peer Reviewed
• [Journal Article] Development of a focal cerebral cooling system for the treatment of intractable epilepsy: An experimental study in cats and non-human primates (2011)
  • Author(s): Takao Inoue, Masami Fujii, Yeting He, Yuichi Maruta, Hiroyuki Kida, Sadahiro Nomura et al.,
  • Journal Title: The 2011 IEEE International Conference on Systems, Man, and Cybernetics Volume: SMC 2011 Pages: 691-695
  • Peer Reviewed
• [Journal Article] 経度低温はTLR2 活性化マイクログリアの NF- κ B 活性化阻害を介と炎症性・抗炎症性因子産生を制御する (2011)
  • Author(s): 松井 智浩、田崎 萌、吉岡 貴裕、本木 由香里、野島 順三、木田 裕之
  • Journal Title: 神経外傷 Volume: 34 Pages: 218-220
  • Peer Reviewed
• [Presentation] てんかんモデルラットにおける局所脳冷却の脳波周波数解析 (2012)
  • Author(s): 木田裕之、藤井正美、井上貴雄、賀業霆、丸田雄一、野村貞宏、谷口和博、市川琢也、斉藤俊、山川烈、鈴木倫保
  • Organizer: 第6回日本てんかん学会中国・四国地方大会
  • Place of Presentation: 高知市文化プラザかるぽーと(高知)
  • Year and Date: 2012-02-11
• [Presentation] てんかんモデルラットにおける局所脳冷却の脳波周波数解析 (2012)
  • Author(s): 木田裕之 et al.
  • Organizer: 第6回日本てんかん学会中国・四国地方会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知）
  • Year and Date: 2012-02-11
• [Presentation] The effect of hypothermia on the laminar disruption and neural injury in neonatal mice following ischemic injury (2012)
  • Author(s): Hiroyuki Kida, Sadahiro Nomura, Mizuya Shinoyama, Makoto Ideguchi, Yuji Owada and Michiyasu Suzuki
  • Organizer: 42th. Soc Neurosci
  • Place of Presentation: New Orleans, USA
• [Presentation] Focal brain cooling suppresses periodic epileptifrom discharges and lessens brain injury after focal cerebral ischemia in rats (2012)
  • Author(s): 賀業霆、藤井正美、井上貴雄、野村貞宏、木田裕之、丸田雄一、国次一郎、山川烈、鈴木倫保
  • Organizer: 第46回日本てんかん学会(JES2012)
  • Place of Presentation: 都市センターホテル(東京)
• [Presentation] 新生児低酸素虚血障害による低体温療法の効果の検討 (2012)
  • Author(s): 木田裕之、野村貞宏、篠山瑞也、出口誠、大和田祐二、鈴木倫保
  • Organizer: 第35回日本神経科学会
  • Place of Presentation: 名古屋国際会議場(名古屋)
• [Presentation] 低酸素性虚血脳障害由来マイクログリアの炎症性および抗炎症性サイトカイン産生に及ぼす軽度低温の影響 (2012)
  • Author(s): 松井智浩、伊波琢也、小原旅人、木田裕之、野村貞宏、鈴木倫保
  • Organizer: 第15回日本脳低温療法学会
  • Place of Presentation: 横浜シンポジア(横浜)
• [Presentation] Challenges and Opportunities for development of a focal cooling device for intractable epilepsy (2012)
  • Author(s): Takao Inoue, Masami Fujii, Tatsuji Tokiwa, Yuichi Maruta, Hiroyuki Kida, Yeting He, Toshitaka Yamakawa, Hirochika Imoto, Sadahiro Nomura, Kenichi Hirano, Masanori Niiyama, Hiromi Yamazaki, Yuji Owada, Takeshi Yamakawa, and Michiyasu Suzuki
  • Organizer: Korean Epilepsy Congress (KEC2012)
  • Place of Presentation: Songdo Convensia, incheon, Korea
• [Presentation] The effect of hypothermia on the laminar disruption and neural injury in neonatal mice following ischemic injury. (2012)
  • Author(s): Hiroyuki Kida
  • Organizer: 42th. Soc Neurosci.
  • Place of Presentation: New Orleans (USA)
• [Presentation] 新生児低酸素虚血障害による低体温療法の効果の検討 (2012)
  • Author(s): 木田裕之
  • Organizer: 第35回日本神経科学会
  • Place of Presentation: 名古屋 (名古屋国際会議場)
• [Presentation] 低酸素性虚血脳障害由来マイクログリアの炎症性および抗炎症性サイトカイン産生に及ぼす軽度低温の影響 (2012)
  • Author(s): 木田裕之
  • Organizer: 第15回 日本脳低温療法学会
  • Place of Presentation: 横浜（横浜シンポジア）
• [Presentation] Focal brain cooling suppresses periodic epileptifrom discharges and lessens brain injury after focal cerebral ischemia in rats (2012)
  • Author(s): 木田裕之
  • Organizer: 第46回日本てんかん学会(JES2012)
  • Place of Presentation: 東京（都市センターホテル）
• [Presentation] Frequency spectrum analysis of electroencephalograms during focal brain cooling in experimental neocortical seizures (2011)
  • Author(s): Kazuhiro Taniguchi, Takuya Ichikawa, Hiroyuki Kida, Masami Fujii, Takao Inoue, Yeting He, Yuichi Maruta, Sadahiro Nomura, Michiyasu Suzuki, Takeshi Yamakawa, Takashi Saito
  • Organizer: 65th American Epilepsy Society Annual Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2011-12-03
• [Presentation] Frequency spectrum analysis of electroencephalograms during focal brain cooling in experimental neocortical seizures (2011)
  • Author(s): Taniguchi et al.
  • Organizer: 65th American Epilepsy Society Annual Meeting
  • Place of Presentation: America (Baltimore)
  • Year and Date: 2011-12-03
• [Presentation] TLR2 活性化マイクログリアの NF- κ B 活性化と炎症性・抗炎症性因子産生の時系列的温度依存性変化 (2011)
  • Author(s): 松井智浩 et al.
  • Organizer: 第14回 日本脳低温療法学会
  • Place of Presentation: かごしま県民交流センター（鹿児島）
  • Year and Date: 2011-07-02
• [Presentation] The effect of focal brain cooling on epileptic discharges in rats: Frequency analysis of electroencephalography (2011)
  • Author(s): Hiroyuki Kida, Masami Fujii, Takao Inoue, Yeting He, Yuichi Maruta, Sadahiro Nomura, Kazuhiro Taniguchi, Takuya Ichikawa, Takashi Saito, Takeshi Yamakawa, and Michiyasu Suzuki
  • Organizer: The 2011 IEEE International Conference on Systems, Man, and Cybernetics
  • Place of Presentation: Alaska, USA
• [Presentation] Development of a focal cerebral cooling system for the treatment of intractable epilepsy: An experimental study in cats and non-human primates (2011)
  • Author(s): Takao Inoue, Masami Fujii, Yeting He, Yuichi Maruta, Hiroyuki Kida, Sadahiro Nomura, Tatsuji Tokiwa, Toshitaka Yamakawa, Kenichi hirano, Masanori Niiyama, Hiromi Yamazaki, Takeshi Yamakawa, and Michiyasu Suzuki
  • Organizer: The 2011 IEEE International Conference on Systems, Man, and Cybernetics
  • Place of Presentation: Alaska, USA
• [Remarks] ホームページ
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~seiri2/index.html