DAMPs as vasospasm and DCI after SAH.

2019 Fiscal Year Annual Research Report

• Project/Area Number: 16K10746
• Research Institution: Kurume University
• Principal Investigator: 菊池 清志 久留米大学, 医学部, 講師 (60404539)
• Co-Investigator(Kenkyū-buntansha): 丸山 征郎 鹿児島大学, 医歯学総合研究科, 特任教授 (20082282) ; 森岡 基浩 久留米大学, 医学部, 教授 (20295140) ; 田中 永一郎 久留米大学, 医学部, 教授 (80188284) ; 森元 陽子 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (30437967)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: クモ膜下出血 / 予防的運動 / DAMPs

Outline of Annual Research Achievements

脳卒中患者の転帰は、発症前の身体活動量に左右される。我々は、これまで、様々なラット脳卒中モデルで、予防的運動 (Preconditioning exercise) の効果を検証してきた。他方、脳卒中患者の予後には、DAMPs (damage associated molecular patterns) や酸化ストレスなどが関与するといわれている。今回、ラットSAH (subarachnoid hemorrhage:クモ膜下出血) モデルを用い、DAMPsや酸化ストレスに対する予防的運動の効果を評価した。
3週間のPreconditioning exerciseを行うことによって、SAH発症後の意識障害、運動障害、感覚障害の軽減が認められた。さらにPreconditioning Exercise群では、坑酸化経路 [Nrf2 (Nuclear factor erythroid 2-related factor 2)/HO-1(ヘムオキシゲナーゼ)] の活性化、酸化ストレスの指標である4HNE (4-Hydroxynonenal) やNT (Nitrotyrosine) の発現量低下、内因性保護タンパク 14-3-3γの発現量増加、アポトーシスに関連するBaxやCaspase 3の活性化の抑制、代表的なDAMPs の一つとして認識されているHMGB1 (High Mobility Group Box 1) の細胞質における発現量低下がみられた。
これらの成果を広く公表すべく、英語論文の執筆を進めている。

Research Products

• [Journal Article] Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. (2020)
  • Author(s): Takada S, Sakakima H, Matsuyama T, Otsuka S, Nakanishi K, Norimatsu K, Itashiki Y, Tani A, Kikuchi K.
  • Journal Title: J Neuroinflammation. Volume: 17 Pages: －
  • DOI: 10.1186/s12974-020-1709-8.
  • Peer Reviewed / Open Access
• [Journal Article] Preconditioning exercise reduces brain damage and neuronal apoptosis through enhanced endogenous 14-3-3γ after focal brain ischemia in rats. (2019)
  • Author(s): Otsuka S, Sakakima H, Terashi T, Takada S, Nakanishi K, Kikuchi K.
  • Journal Title: Brain Struct Funct. Volume: 224 Pages: 727-738
  • DOI: 10.1007/s00429-018-1800-4.
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. (2019)
  • Author(s): Terashi T, Otsuka S, Takada S, Nakanishi K, Ueda K, Sumizono M, Kikuchi K, Sakakima H.
  • Journal Title: Neurol Res. Volume: 41 Pages: 510-518
  • DOI: 10.1080/01616412.2019.1580458.
  • Peer Reviewed
• [Journal Article] Antioxidant and Anti-Inflammatory Properties of Anthocyanins Extracted from Oryza sativa L. in Primary Dermal Fibroblasts (2019)
  • Author(s): Palungwachira P, Tancharoen S, Phruksaniyom C, Klungsaeng S, Srichan R, Kikuchi K, Nararatwanchai T.
  • Journal Title: Oxid Med Cell Longev. Volume: － Pages: －
  • DOI: 10.1155/2019/2089817.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Growth Hormone Biosynthesis by Cdk5 Regulatory Subunit Associated Protein 1-like 1 (CDKAL1) in Pituitary Adenomas (2019)
  • Author(s): Takesue Y, Wei FY, Fukuda H, Tanoue Y, Yamamoto T, Chujo T, Shinojima N, Yano S, Morioka M, Mukasa A, Kuratsu J, Tomizawa K.
  • Journal Title: Endocr J . Volume: 66 Pages: 807-816.
  • DOI: 10.1507/endocrj.EJ18-0536.
  • Peer Reviewed / Open Access
• [Journal Article] Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas. (2019)
  • Author(s): Komaki S, Sugita Y, Furuta T, Yamada K, Moritsubo M, Abe H, Akiba J, Miyagi N, Nakamura H, Miyoshi H, Ohshima K, Morioka M.
  • Journal Title: J Neuropathol Exp Neurol. Volume: 78 Pages: 389-397
  • DOI: 10.1093/jnen/nly124.
  • Peer Reviewed / Open Access
• [Journal Article] Leptomeningeal Carcinomatosis After Neoplastic Cerebral Aneurysm Rupture. (2019)
  • Author(s): Koga M, Aoki T, Negoto T, Makizono T, Sugi K, Fujimori K, Kajiwara S, Komaki S, Yoshitomi M, Sugita Y, Morioka M.
  • Journal Title: World Neurosurg Volume: 126 Pages: 281-284
  • DOI: 10.1016/j.wneu.2019.02.058.
  • Peer Reviewed / Open Access
• [Journal Article] Leakage sign for acute subdural hematoma in clinical treatment. (2019)
  • Author(s): Yamamoto M, Orito K, Nakamura Y, Takeshige N, Yoshitomi M, Takeuchi Y, Uzu H, Takasu O, Abe T, Tanoue S, Uchiyama Y, Morioka M.
  • Journal Title: Acta Neurochir (Wien). Volume: 161 Pages: 233-238
  • DOI: 10.1007/s00701-018-3755-x.
  • Peer Reviewed / Open Access
• [Journal Article] Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review. (2019)
  • Author(s): Sugita Y, Furuta T, Komaki S, Ohshima K, Sakata K, Morioka M.
  • Journal Title: Neuropathology Volume: 39 Pages: 120-126
  • DOI: 10.1111/neup.12533.
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia. (2019)
  • Author(s): Noguchi K, Ali TFS, Miyoshi J, Orito K, Negoto T, Biswas T, Taira N, Koga R, Okamoto Y, Fujita M, Otsuka M, Morioka M.
  • Journal Title: Eur J Med Chem. Volume: 63 Pages: 207-214
  • DOI: 10.1016/j.ejmech.2018.11.060.
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic Endonasal Removal of Primary/Recurrent Meningiomas in the Medial Optic Canal: Surgical Technique and Long-Term Visual Outcome (2019)
  • Author(s): Sakata K, Takeshige N, Nagata Y, Yoshitake H, Komaki S, Miyagi N, Morioka M.
  • Journal Title: Oper Neurosurg (Hagerstown). Volume: 17 Pages: 470-480
  • DOI: 10.1093/ons/opz001.
  • Peer Reviewed
• [Journal Article] Sagittal diffusion-weighted imaging in preventing the false-negative diagnosis of acute brainstem infarction: Confirmation of the benefit by anatomical characterization of false-negative lesions. (2019)
  • Author(s): Takeshige N, Aoki T, Sakata K, Kajiwara S, Negoto T, Nagase S, Tanoue S, Uchiyama Y, Hirohata M, Abe T, Morioka M.
  • Journal Title: Surg Neurol Int. Volume: 10 Pages: －
  • DOI: 10.25259/SNI_182_2019.
  • Peer Reviewed / Open Access
• [Journal Article] Deep Cervical Artery as a Source of Bleeding in Postoperative Spinal Epidural Hematoma: A Case Report. (2019)
  • Author(s): Koga M, Hattori G, Maeda M, Nakamura Y, Miyagi T, Okura A, Morioka M, Uchikado H.
  • Journal Title: NMC Case Rep J. Volume: 6 Pages: 87-90
  • DOI: 10.2176/nmccrj.cr.2018-0214.
  • Peer Reviewed / Open Access
• [Journal Article] Gamma knife surgery-induced aneurysm rupture associated with tissue plasminogen activator injection: A case report and literature review. (2019)
  • Author(s): Kikuchi J, Takeuchi Y, Sugi K, Negoto T, Yoshitomi M, Hirohata M, Morioka M.
  • Journal Title: Surg Neurol Int. Volume: 10 Pages: －
  • DOI: 10.25259/SNI_210_2019.
  • Peer Reviewed / Open Access
• [Journal Article] N-glycome inheritance from cells to extracellular vesicles in B16 melanomas. (2019)
  • Author(s): Harada Y, Kizuka Y, Tokoro Y, Kondo K, Yagi H, Kato K, Inoue H, Taniguchi N, Maruyama I.
  • Journal Title: FEBS Lett. Volume: 593 Pages: 942-951
  • DOI: 10.1002/1873-3468.13377.
  • Peer Reviewed / Open Access
• [Journal Article] Generation of the heterogeneity of extracellular vesicles by membrane organization and sorting machineries. (2019)
  • Author(s): Harada Y, Suzuki T, Fukushige T, Kizuka Y, Yagi H, Yamamoto M, Kondo K, Inoue H, Kato K, Taniguchi N, Kanekura T, Dohmae N, Maruyama I.
  • Journal Title: Biochim Biophys Acta Gen Subj. Volume: 1863 Pages: 681-691
  • DOI: 10.1016/j.bbagen.2019.01.015.
  • Peer Reviewed
• [Journal Article] Application of high-mannose-type glycan-specific lectin from Oscillatoria Agardhii for affinity isolation of tumor-derived extracellular vesicles. (2019)
  • Author(s): Yamamoto M, Harada Y, Suzuki T, Fukushige T, Yamakuchi M, Kanekura T, Dohmae N, Hori K, Maruyama I.
  • Journal Title: Anal Biochem. Volume: 580 Pages: 21-29
  • DOI: 10.1016/j.ab.2019.06.001.
  • Peer Reviewed
• [Journal Article] Recombinant Thrombomodulin Suppresses Histone-Induced Neutrophil Extracellular Trap Formation. (2019)
  • Author(s): Shrestha B, Ito T, Kakuuchi M, Totoki T, Nagasato T, Yamamoto M, Maruyama I.
  • Journal Title: Front Immunol. Volume: 10 Pages: －
  • DOI: 10.3389/fimmu.2019.02535.
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation. (2019)
  • Author(s): Namino F, Yamakuchi M, Iriki Y, Okui H, Ichiki H, Maenosono R, Oketani N, Masamoto I, Miyata M, Horiuchi M, Hashiguchi T, Ohishi M, Maruyama I.
  • Journal Title: Clin Appl Thromb Hemost. Volume: 25 Pages: －
  • DOI: 10.1177/1076029619851570.
  • Peer Reviewed / Open Access
• [Journal Article] Immunological evidence for in vivo production of novel advanced glycation end-products from 1,5-anhydro-D-fructose, a glycogen metabolite. (2019)
  • Author(s): Sakasai-Sakai A, Takata T, Suzuki H, Maruyama I, Motomiya Y, Takeuchi M.
  • Journal Title: Sci Rep. Volume: 9 Pages: －
  • DOI: 10.1038/s41598-019-46333-2.
  • Peer Reviewed / Open Access
• [Journal Article] Serum histone H3 levels and platelet counts are potential markers for coagulopathy with high risk of death in septic patients: a single-center observational study. (2019)
  • Author(s): Ito T, Totoki T, Yokoyama Y, Yasuda T, Furubeppu H, Yamada S, Maruyama I, Kakihana Y.
  • Journal Title: J Intensive Care. Volume: 7 Pages: －
  • DOI: 10.1186/s40560-019-0420-2.
  • Peer Reviewed / Open Access
• [Journal Article] Circulating histone H3 levels in septic patients are associated with coagulopathy, multiple organ failure, and death: a single-center observational study. (2019)
  • Author(s): Yokoyama Y, Ito T, Yasuda T, Furubeppu H, Kamikokuryo C, Yamada S, Maruyama I, Kakihana Y.
  • Journal Title: Thromb J. Volume: 17 Pages: －
  • DOI: 10.1186/s12959-018-0190-4.
  • Peer Reviewed / Open Access
• [Journal Article] Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing. (2019)
  • Author(s): Yamada S, Hirao D, Miura N, Iwanaga T, Kawaguchi T, Yoshimura A, Oomori T, Nagasato T, Maruyama I, Fukushima R.
  • Journal Title: Exp Anim. Volume: 68 Pages: 137-146
  • DOI: 10.1538/expanim.18-0100.
  • Peer Reviewed / Open Access
• [Journal Article] Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: an exploratory observational study. (2019)
  • Author(s): Yamamoto K, Ito T, Nagasato T, Shinnakasu A, Kurano M, Arimura A, Arimura H, Hashiguchi H, Deguchi T, Maruyama I, Nishio Y.
  • Journal Title: Thromb J. Volume: 17 Pages: －
  • DOI: 10.1186/s12959-019-0206-8.
  • Peer Reviewed / Open Access
• [Presentation] 尿酸は rtPA線溶効果を増強するか?― 脳梗塞急性期治療における閉塞血管の再開通率向上を目指して― (2019)
  • Author(s): 菊池 清志
  • Organizer: 第19回 TTMフォーラム
  • Invited
• [Presentation] ラット椎弓切除モデルにおけるE8002の癒着防止効果の検証 (2019)
  • Author(s): 菊池 清志
  • Organizer: 第28回 脳神経外科手術と機器学会 (CNTT)
• [Presentation] Application of a Novel Anti-Adhesive Membrane, E8002, in an experimental model of peripheral nerve adhesion in rats. (2019)
  • Author(s): 菊池 清志
  • Organizer: 第34回日本脊髄外科学会