Intracranial aneurysms related to periodontal disease in basic- and clinical studies

• Project/Area Number: 17K10832
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: KANEMATSU Yasuhisa 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (90363142)
• Co-Investigator(Kenkyū-buntansha): 多田 恵曜 徳島大学, 病院, 特任講師 (30547964) ; 島田 健司 徳島大学, 病院, 特任講師 (60624351) ; 高麗 雅章 徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (60794013) ; 八木 謙次 川崎医科大学, 医学部, 講師 (80551837)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脳 / くも膜下出血 / 歯周病菌 / 高血圧 / 脳・神経 / 血管障害 / 頚動脈病変 / 脳動脈瘤破裂 / 脳血管病 / エストロゲン / 歯周病 / 脳動脈瘤

Outline of Final Research Achievements

Although a relationship between subarachnoid hemorrhage (SAH) and periodontal disease (PD) has been suggested, it remains unclear. To study how IA and SAH are associated with PD and which periodontal pathogens affect them, we studied prospectively, consecutive patients with ruptured and unruptured IAs and the controls without cerebrovascular disorders and evaluated using the Community Periodontal Index of Treatment Needs by a dentist and the DNA levels of subgingival bacteria in PD and plasma.
Although no rupture-specific bacteria were identified, the positive rate of DNA of subgingival bacteria in plaque was significantly higher in patients with severe PD and hypertension than the other groups. The plasma level of matrix metalloproteinase-9 was significantly higher in severe PD patients with ruptured IAs than the controls. Local inflammation by periodontal bacteria may lead to not only severe PD but also systemic inflammation.

Academic Significance and Societal Importance of the Research Achievements

脳動脈破裂によるくも膜下出血（SAH）は、予後が重篤で、寝たきり原因の国内第一位となっているため、多角的な原因究明と有効な治療法が切望されている。
歯周病は血管障害のない健常者でも認められるが、SAHへの影響は不明である。臨床研究において、高血圧に重症歯周病が合併すると破裂率が有意に高いことを見出した。また歯周病診断におけるBleeding on probing(BOP)の指標が高い症例が重症歯周病と関係しており、血中の炎症マーカー、特にマトリックスメタロプロテアーゼの上昇とも関係することを見出している。さらに歯周病による血管障害と関連したメカニズムを検討中である。

Research Products

• [Journal Article] Activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons (2019)
  • Author(s): Hioka Akemi、Tada Yoshiteru、Kitazato Keiko、Kanematsu Yasuhisa、Mizobuchi Yoshifumi、Mure Hideo、Shimada Kenji、Okazaki Toshiyuki、Korai Masaaki、Akazawa Naoki、Matsumoto Yuki、Harada Masafumi、Takagi Yasushi、Nagahiro Shinji
  • Journal Title: Journal of Clinical Neuroscience Volume: 60 Pages: 79-83
  • DOI: 10.1016/j.jocn.2018.09.035
  • Peer Reviewed / Open Access
• [Journal Article] Time-dependent and site-dependent morphological changes in rupture-prone arteries: ovariectomized rat intracranial aneurysm model (2019)
  • Author(s): Yamaguchi Tadashi、Miyamoto Takeshi、Kitazato Keiko T.、Shikata Eiji、Yamaguchi Izumi、Korai Masaaki、Shimada Kenji、Yagi Kenji、Tada Yoshiteru、Matsuzaki Yoshihito、Kanematsu Yasuhisa、Takagi Yasushi
  • Journal Title: Journal of Neurosurgery Volume: - Issue: 5 Pages: 1-9
  • DOI: 10.3171/2019.6.jns19777
  • NAID: 120006880916
  • Peer Reviewed / Open Access
• [Journal Article] Active Cancer and Elevated D-Dimer Are Risk Factors for In-Hospital Ischemic Stroke (2019)
  • Author(s): Yamaguchi I, Kanematsu Y, Shimada K, Korai M, Miyamoto T, Shikata E, Yamaguchi T, Yamamoto N, Yamamoto Y, Kitazato KT, Okayama Y, Takagi Y
  • Journal Title: Cerebrovas Dis Extra Volume: 9(3) Issue: 3 Pages: 129-138
  • DOI: 10.1159/000504163
  • NAID: 120007001423
  • Peer Reviewed / Open Access
• [Journal Article] Importance of Managing the Water-Electrolyte Balance by Delivering the Optimal Minimum Amount of Water and Sodium After Subarachnoid Hemorrhage (2019)
  • Author(s): Shikata Eiji、Tamura Tetsuya、Shinno Kiyohito、Okayama Yoshihiro、Shinohara Naoki、Shimada Kenji、Kanematsu Yasuhisa、Kitazato Keiko T.、Nagahiro Shinji、Takagi Yasushi
  • Journal Title: World Neurosurgery Volume: 129 Pages: e352-e360
  • DOI: 10.1016/j.wneu.2019.05.152
  • Peer Reviewed
• [Journal Article] Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study (2018)
  • Author(s): 1.Nagahiro S, Tada Y, Satomi J, Kinouchi T, Kuwayama K, Yagi K, Nakajima K, Matsushita N, Miyamoto T, Yamaguchi T, Shimada K, Korai M, Mure H, Okayama Y, Abe T, Harada M, Kitazato KT, Kanematsu Y
  • Journal Title: Stroke Cerebrovasc Dis Volume: - Issue: 8 Pages: 2134-2140
  • DOI: 10.1016/j.jstrokecerebrovasdis.2018.03.008
  • NAID: 120006961144
  • Peer Reviewed / Open Access
• [Journal Article] Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment (2017)
  • Author(s): Sogabe S, Satomi J, Tada Y, Kanematsu Y, Kuwayama K, Yagi K, Yoshioka S, Mizobuchi Y, Mure H, Yamaguchi I, Abe T, Yamamoto N, Kitazato KT, Kaji R, Harada M, Nagahiro S
  • Journal Title: Neuroradiology. Volume: － Issue: 6 Pages: 587-595
  • DOI: 10.1007/s00234-017-1828-9
  • Peer Reviewed / Open Access
• [Journal Article] Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset – Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients (2017)
  • Author(s): Kanematsu Y, Satomi J, Kuwayama K, Yamaguchi I, Yoshioka S, Kinouchi T, Tada Y, Yamamoto N, Matsubara S, Satoh K, Nagahiro S
  • Journal Title: Neurologia medico-chirurgica Volume: 57 Issue: 6 Pages: 278-283
  • DOI: 10.2176/nmc.oa.2016-0236
  • NAID: 130006882460
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Open Access
• [Presentation] Downregulation of estrogen receptor alpha activates NLRP3 inflammasome in a rat model of intracranial aneurysms (2019)
  • Author(s): Yamaguchi T, KT.Kitazato, Eiji Shikata, Takeshi Miyamoto, Masaaki Korai,Kenji Shimada, Yoshiteru Tada, Yasuhisa Kanematsu, Yasushi Takagi
  • Organizer: International Stroke Conference
  • Int'l Joint Research