Development of new theraphy of brain protection, dementia prevention and neuroregeneration focusing on astrocytes in cerebral infarction

• Project/Area Number: 15K09316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: Deguchi Kentaro 岡山大学, 医学部, 客員研究員 (80467753)
• Co-Investigator(Kenkyū-buntansha): 太田 康之 岡山大学, 大学病院, 講師 (20746854) ; 菱川 望 岡山大学, 大学病院, 助教 (90378175)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 脳血管障害 / 低酸素ストレス / 酸化ストレス / アストロサイト / 脳梗塞 / 脳組織保護

Outline of Final Research Achievements

In this study, we focused on the role of astrocytes in hypoxia and oxidative stress of cerebral infarction, and analyzed it using mouse focal cerebral ischemia model. Immunohistochemistry of cerebral tissue sections showed remarkable increased expression of HIF1α, a hypoxic stress marker, around the cerebral infarction lesions 12 hours after the cerebral infarction, and the highest expression of GSH, antioxidant stress marker, 72 hours after the onset of cerebral infarction. In vivo imaging and on immunohistochemical analyses, the expression of Nrf2, an oxidative stress marker, peaked after 24 hours, and Nrf2 was expressed in both neurons and astrocytes. This study suggested that hypoxic stress was first involved in cerebral infarction, then oxidative stress was involved, in which astrocyte acted mainly.

Research Products

• [Journal Article] Time-dependent change of in vivo optical imaging of oxidative stress in a mouse stroke model. (2017)
  • Author(s): Nakano Y, Yamashita T, Li Q, Sato K, Ohta Y, Morihara R, Hishikawa N, Abe K.
  • Journal Title: J Neurosci Res. Volume: 印刷中 Issue: 10 Pages: 2030-2039
  • DOI: 10.1002/jnr.24047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neuroprotective Effects of a Novel Antioxidant Mixture Twendee X in Mouse Stroke Model. (2017)
  • Author(s): Kusaki M, Ohta Y, Inufusa H, Yamashita T, Morihara R, Nakano Y, Liu X, Shang J, Tian F, Fukui Y, Sato K, Takemoto M, Hishikawa N, Abe K.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: 印刷中 Issue: 6 Pages: 1191-1196
  • DOI: 10.1016/j.jstrokecerebrovasdis.2017.01.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection (2017)
  • Author(s): Morihara R, Yamashita T, Deguchi K, Tsunoda K, Manabe Y, Takahashi Y, Yunoki T, Sato K, Nakano Y, Kono S, Ohta Y, Hishikawa N, Abe K
  • Journal Title: Internal Medicine Volume: 56 Issue: 17 Pages: 2343-2346
  • DOI: 10.2169/internalmedicine.8438-16
  • NAID: 130006039391
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat. (2016)
  • Author(s): Li Q, Ohta Y, Yamashita T, Shang J, Deguchi K, Feng T, Sato K, Hishikawa N, Nakano Y, Abe K.
  • Journal Title: J Neurosci Res. Volume: 印刷中 Issue: 9 Pages: 1745-1759
  • DOI: 10.1002/jnr.24005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2. (2016)
  • Author(s): Morihara R, Yamashita T, Kono S, Shang J, Nakano Y, Sato K, Hishikawa N, Ohta Y, Heitmeier S, Perzborn E, Abe K.
  • Journal Title: J Neurosci Res. Volume: 印刷中 Issue: 9 Pages: 1818-1828
  • DOI: 10.1002/jnr.24013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Temporal Profiles of Stress Protein Inductions after Focal Transient Ischemia in Mice Brain. (2016)
  • Author(s): Li Q, Nakano Y, Shang J, Ohta Y, Sato K, Takemoto M, Hishikawa N, Yamashita T, Abe K.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: Oct;25(10): Issue: 10 Pages: 2344-2351
  • DOI: 10.1016/j.jstrokecerebrovasdis.2016.05.031
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Telmisartan promotes potential glucose homeostasis in stroke-resistant spontaneously hypertensive rats via peroxisome proliferator-activated receptor γ activation (2015)
  • Author(s): Omote Y, Deguchi K, Kurata T, Yamashita T, Sato K, Hishikawa N, Abe K
  • Journal Title: Curr Neurovasc Res Volume: 12 Pages: 91-97
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2. (2017)
  • Author(s): Morihara R, Yamashita T, Kono S, Shang J, Nakano Y, Sato K, Hishikawa N, Ohta Y, Heitmeier S, Perzborn E, Abe K
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] tPA4.5時間時代の急性期脳梗塞治療 (2017)
  • Author(s): 森原隆太、河野祥一郎、佐藤恒太、太田康之、菱川望、山下徹、出口健太郎、真邊泰宏、高尾芳樹、柏原健一、桐山英樹、阿部康二
  • Organizer: 第17回日本抗加齢医学会総会
• [Presentation] 血栓溶解療法後の頭蓋内出血に対するリバーロキサバンのPARを介した抑制効果 (2017)
  • Author(s): 森原隆太、山下徹、河野祥一郎、商敬偉、中野由美子、佐藤恒太、菱川望、太田康之、阿部康二
  • Organizer: 第8回日本脳血管・認知症学術大会
• [Presentation] 前方、後方循環別に比較した症状悪化を伴うBranch atheromatous disease (BAD) の特徴 (2017)
  • Author(s): 高橋義秋、山下徹、森原隆太、中野由美子、商敬偉、佐藤恒太、武本麻美、菱川望、太田康之、阿部康二
  • Organizer: 第15回日本臨床医療福祉学会
• [Presentation] 岡山大学関連病院における超高齢者超急性期脳梗塞に対するt-PA静注療法の臨床的検討 (2017)
  • Author(s): 角田慶一郎、山下徹、河野祥一郎、出口健太郎、倉田智子、真邊泰宏、高尾芳樹、河田幸波、柏原健一、井上智、桐山英樹、阿部康二
  • Organizer: 第7回日本認知症予防学会学術集会
• [Presentation] The pathological role of TDP-43 and NF-kb in mild cognitive impairment and Alzheimer's disease (2016)
  • Author(s): Ohta Y, Tremblay C, Schneider JA, Bennett DA, Calon F, Julien JP, Abe K
  • Organizer: AAIC2016
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] 高血圧ラット(SHR-SR)におけるテルミサルタンの抗酸化ストレス作用とαシヌクレイン蓄積に対する効果の検討 (2015)
  • Author(s): 福井裕介、菱川 望、佐藤恒太、河野祥一郎、太田康之、山下 徹、出口健太郎、阿部康二
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: 青森
  • Year and Date: 2015-10-02