Clarifying the pathophysiology of early brain injury after subarachnoid hemorrhage focusing on matricellular proteins.

• Project/Area Number: 25861272
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Mie University
• Principal Investigator: SHIBA Masato 三重大学, 医学部附属病院, 診療等従事者 (30595682)
• Research Collaborator: SUZUKI Hidenori ; FUJIMOTO Masashi ; KAWAKITA Fumihiro
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: くも膜下出血 / 早期脳損傷 / マトリセル蛋白 / テネイシンC / MAPキナーゼ / アポトーシス / 脳損傷

Outline of Final Research Achievements

We investigated the effect of tenascin-C(TNC), a matricellular protein, on pathophysiology of early brain injury after experimental subarachnoid hemorrhage(SAH) by using rats and mice endovascular perforation models. Firstly, we showed that SAH caused neuronal apoptosis in the brain with TNC upregulation. Next, we showed that intracisternally injected recombinant TNC reversed the anti-apoptotic effects in brain by imatinib. Lastly, using various inhibitors, we showed that early brain injury was improved with inhibition of TNC upregulation by supression of MAP kinase-dependent MMP-9 induction.

Research Products

• [Journal Article] The Role of Matricellular Proteins in Brain Edema after Subarachnoid Hemorrhage (2016)
  • Author(s): Suzuki H, Fujimoto M, Shiba M, Kawakita F, Liu L, Ichikawa N, Kanamaru K, Imanaka-Yoshida K, Yoshida T
  • Journal Title: Acta Neurochir Suppl Volume: 121 Pages: 151-156
  • DOI: 10.1007/978-3-319-18497-5_27
  • ISBN: 9783319184968, 9783319184975
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice. (2015)
  • Author(s): Fujimoto M, Shiba M, Kawakita F, Liu L, Shimojo N, Imanaka-Yoshida K, Yoshida T, Suzuki H.
  • Journal Title: J Neurosurg Volume: 16 Issue: 6 Pages: 1-10
  • DOI: 10.3171/2015.4.jns15484
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of tenascin-C on early brain injury after subarachnoid hemorrhage in rats (2015)
  • Author(s): Shiba M, Fujimoto M, Kawakita F, Imanaka-Yoshida K, Yoshida T, Kanamaru K, Taki W, Suzuki H
  • Journal Title: Acta Neurochir Suppl Volume: 120 Pages: 69-73
  • DOI: 10.1007/978-3-319-04981-6_12
  • ISBN: 9783319049809, 9783319049816
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vasoconstrictive effect of tenascin-C on cerebral arteries in rats. (2015)
  • Author(s): Fujimoto M, Shiba M, Kawakita F, Shimojo N, Imanaka-Yoshida K, Yoshida T, Kanamaru K, Taki W, Suzuki H.
  • Journal Title: Acta Neurochir Suppl Volume: 120 Pages: 99-103
  • DOI: 10.1007/978-3-319-04981-6_17
  • ISBN: 9783319049809, 9783319049816
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (2015)
  • Author(s): Suzuki H, Kanamaru K, Shiba M, Fujimoto M, Kawakita F, Imanaka-Yoshida K, Yoshida T, Taki W
  • Journal Title: Acta Neurochir Suppl Volume: 120 Pages: 117-121
  • DOI: 10.1007/978-3-319-04981-6_20
  • ISBN: 9783319049809, 9783319049816
  • Peer Reviewed
• [Journal Article] Tenascin-C causes neuronal apoptosis after subarachnoid hemorrhage in rats. (2014)
  • Author(s): Tenascin-C causes neuronal apoptosis after subarachnoid hemorrhage in rats. Shiba M, Fujimoto M, Imanaka-Yoshida K, Yoshida T, Taki W, Suzuki H.
  • Journal Title: Transl Stroke Res. Volume: 5 Issue: 2 Pages: 238-247
  • DOI: 10.1007/s12975-014-0333-2
  • Peer Reviewed
• [Journal Article] Matricellular protein: a new player in cerebral vasospasm following subarachnoid hemorrhage (2013)
  • Author(s): Hidenori Suzuki, et al
  • Journal Title: Acta Neurochir Suppl Volume: 115 Pages: 213-218
  • DOI: 10.1007/978-3-7091-1192-5_39
  • ISBN: 9783709111918, 9783709111925
  • Peer Reviewed
• [Journal Article] Role of platelet-derived growth factor in cerebral vasospasm after subarachnoid hemorrhage in rats (2013)
  • Author(s): Masato Shiba, Hidenori Suzuki, et al
  • Journal Title: Acta Neurochir Suppl Volume: 115 Pages: 219-223
  • DOI: 10.1007/978-3-7091-1192-5_40
  • ISBN: 9783709111918, 9783709111925
  • Peer Reviewed
• [Journal Article] Tenascin-C induces prolonged constriction of cerebral arteries in rats (2013)
  • Author(s): Masashi Fujimoto, Hidenori Suzuki, et al
  • Journal Title: Neurobiol Dis Volume: - Pages: 104-109
  • DOI: 10.1016/j.nbd.2013.01.007
  • Peer Reviewed
• [Presentation] Role of tenascin-C in early brain injury : Evaluation using tenascin-C knockout mice (2015)
  • Author(s): Masashi Fujimoto, Masato Shiba, Fumihiro Kawakita, Lei Liu, Naoshi Shimojo, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Hidenori Suzuki
  • Organizer: Vasospasm2015
  • Place of Presentation: 軽井沢プリンスホテルウエスト（長野県軽井沢市）
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] The role of matricellular proteins in brain edema after experimental subarachnoid hemorrhage (2014)
  • Author(s): Hidenori Suzuki, Masashi Fujimoto, Masato Shiba, Fumihiro Kawakita, Liu Lei, Naoki Ichikawa, Kenji Kanamaru, Kyoko Imanaka-Yoshida, Toshimichi Yoshida
  • Organizer: The 16th International Conference on Brain Edema and Cellular Injury
  • Place of Presentation: Huntington Beach, CA, USA (Hyatt Regency Huntington Beach Resort and Spa)
  • Year and Date: 2014-09-27 – 2014-09-30
• [Presentation] くも膜下出血後の遅発性脳血管攣縮の病態と治療 (2014)
  • Author(s): 鈴木秀謙、川北文博、劉 磊、市川尚己、藤本昌志、芝 真人
  • Organizer: 第34回日本脳神経外科コングレス総会
  • Place of Presentation: 大阪 (大阪国際会議場)
  • Year and Date: 2014-05-16 – 2014-05-18
  • Invited
• [Presentation] Effects of tenascin-C on early brain injury after subarachnoid hemorrhage in rats (2013)
  • Author(s): Masato Shiba, Masashi Fujimoto, Fumio Kawakita, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Kenji Kanamaru, Waro Taki, Hidenori Suzuki
  • Organizer: The 12th International Conference on Neurovascular Events after Subarachnoid Hemorrhage
  • Place of Presentation: スイス、ルツェルン
• [Presentation] Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (2013)
  • Author(s): Hidenori Suzuki, Kenji Kanamaru, Masato Shiba, Masashi Fujimoto, Fumio Kawakita, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Waro Taki
  • Organizer: The 12th International Conference on Neurovascular Events after Subarachnoid Hemorrhage
  • Place of Presentation: スイス、ルツェルン
• [Presentation] Vasoconstrictive effect of tenascin-C on cerebral arteries in rats (2013)
  • Author(s): Masashi Fujimoto, Masato Shiba, Fumio Kawakita, Kenji Kanamaru, Waro Taki, Hidenori Suzuki
  • Organizer: The 12th International Conference on Neurovascular Events after Subarachnoid Hemorrhage
  • Place of Presentation: スイス、ルツェルン
• [Presentation] Matricellular proteinによるくも膜下出血後脳血管攣縮の制御 (2013)
  • Author(s): 鈴木秀謙、芝 真人、藤本昌志、川北文博、今中恭子、吉田利通
  • Organizer: 第45回日本結合組織学会学術集会・第60回マトリックス研究会大会 合同学術大会
  • Place of Presentation: 和歌山
  • Invited