Exploring a novel therapeutic agent for the treatment of traumatic brain injury based on the function of glial cells

• Project/Area Number: 26450447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Osaka Prefecture University
• Principal Investigator: Moriyama Mitsuaki 大阪府立大学, 生命環境科学研究科, 准教授 (20275283)
• Co-Investigator(Kenkyū-buntansha): 高野 桂 大阪府立大学, 生命環境科学研究科, 准教授 (50453139) ; 中村 洋一 大阪府立大学, 生命環境科学研究科, 教授 (90180413)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 外傷性能損傷 / アストロサイト / 浮腫 / ミクログリア / グリア活性化 / 生理学 / 神経化学 / 外傷性脳損傷 / 国際情報交換

Outline of Final Research Achievements

Cerebral edema is an important complication of traumatic brain injury (TBI) and astrocyte swelling appears to be primarily responsible for the edema. We focused on the activation of glial cells such as astrocytes and microglia in this swelling and searched for inhibitors for the purpose of exploring novel neuroprotective / therapeutic agents. We found that acetate suppressed glial cell activation and reduced edema. Acetate may offer these effects through an anti-oxidative mechanism. The obtained results suggest the possibility of acetate as an effective therapeutic agent for brain edema after TBI.

Research Products

• [Journal Article] Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency. (2017)
  • Author(s): Saheki T, Inoue K, Ono H, Fujimoto Y, Furuie S, Yamamura KI, Kuroda E, Ushikai M, Asakawa A, Inui A, Eto K, Kadowaki T, Moriyama M, Sinasac DS, Yamamoto T, Furukawa T, Kobayashi K.
  • Journal Title: Molecular Genetics and Metabolism Volume: 120 Issue: 4 Pages: 306-316
  • DOI: 10.1016/j.ymgme.2017.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acetate attenuates lipopolysaccharide-induced nitric oxide production through an anti-oxidative mechanism in cultured primary rat astrocytes. (2016)
  • Author(s): Mitsuaki Moriyama, Ryosuke Kurebayashi, Kenji Kawabe, Katsura Takano, Yoichi Nakamura.
  • Journal Title: Neurochemical Research Volume: 41 (11) Issue: 11 Pages: 3138-3146
  • DOI: 10.1007/s11064-016-2038-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mechanism for increased hepatic glycerol synthesis in the citrin/mitochondria glycerol-3-phosphate dehydrogenase double-knockout mouse: Urine glycerol and glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency. (2015)
  • Author(s): Moriyama M, Fujimoto Y, Rikimaru S,Ushikai M, Kuroda E, Kawabe K, Takano K,Asakawa A, Inui A, Eto K, Kadowaki T, Sinasac DS, Okano Y, Yazaki M, Ikeda SI,Zhang C, Song YZ,Sakamoto O, Kure S, Mitsubuchi H, Endo F, Horiuchi M, Nakamura Y, Yamamura KI, Saheki T.
  • Journal Title: Biochim Biophys Acta. Volume: 印刷中 Issue: 9 Pages: 1787-1795
  • DOI: 10.1016/j.bbadis.2015.04.023
  • Peer Reviewed / Open Access
• [Journal Article] Lipopolysaccharide-stimulated transglutaminase 2 expression enhances endocytosis activity in mouse microglial cell line BV-2. (2015)
  • Author(s): Kenji Kawabe, Katsura Takano, Mitsuaki Moriyama, Yoichi Nakamura
  • Journal Title: Neuroimmunomodulation Volume: 22 Issue: 4 Pages: 243-249
  • DOI: 10.1159/000365484
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Theophylline potentiates lipopolysaccharide-induced NO production in cultured astrocytes. (2014)
  • Author(s): Ogawa M, Takano K, Kawabe K, Moriyama M, Ihara H, Nakamura Y.
  • Journal Title: Neurochemical Research Volume: 39 Issue: 1 Pages: 107-116
  • DOI: 10.1007/s11064-013-1195-9
  • Peer Reviewed
• [Journal Article] Amphotericin B Induces Glial Cell Line-Derived Neurotrophic Factor in the Rat Brain (2014)
  • Author(s): Akiko Motoyoshi-Yamashiro, Katsura Takano, Kenji Kawabe, Takeshi Izawa, Hidemitsu Nakajima, Mitsuaki Moriyama, Yoichi Nakamura
  • Journal Title: Journal of Veterinary Medical Science Volume: 76 Issue: 10 Pages: 1353-1358
  • DOI: 10.1292/jvms.14-0160
  • NAID: 130004693905
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Effects of acetate on LPS-induced nitric oxide production in primary rat microglia and BV-2 cell line. (2016)
  • Author(s): Moriyama M, Kawabe K, Hashimoto A, Nishimura Y, Matoba K, Takano K, Nakamura Y.
  • Organizer: 第59回日本神経化学会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-08
• [Presentation] ミクログリアの組織型トランスグルタミナーゼ発現とエンドサイトーシスに対するアンホテリシンBの効果 (2015)
  • Author(s): 河邊憲司, 高野桂, 森山光章, 中村洋一
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市中央区）
  • Year and Date: 2015-12-01
• [Presentation] Acetate attenuates LPS-induced nitric oxide production in cultured astrocytes。 (2015)
  • Author(s): Moriyama M, Kurebayashi R, Kawabe K, Hashimoto A, Takano K, Nakamura Y.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ（埼玉県さいたま市大宮区）
  • Year and Date: 2015-09-11
• [Presentation] シトリン欠損症モデルマウス灌流肝アミノ酸およびTCAサイクル中間体代謝に対する糖質負荷の効果 (2014)
  • Author(s): 森山光章、藤本侑希、牛飼美晴、高野桂、堀内正久、中村洋一、佐伯武頼
  • Organizer: 第56回日本先天代謝異常学会総会
  • Place of Presentation: 東北大学
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] アストロサイトにおけるLPS誘導性NO産生に対する酢酸の抑制効果 (2014)
  • Author(s): 呉林亮祐、森山光章、河邊憲司、高野桂、中村洋一
  • Organizer: 第158回日本獣医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-09-09 – 2014-09-12