Neuroprotective effects of ADAMTS13 against delayed brain ischemia after subarachnoid hemorrhage

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Nara Medical University
• Principal Investigator: Fujioka Masayuki 奈良県立医科大学, 医学部, 非常勤講師 (20254518)
• Co-Investigator(Kenkyū-buntansha): 三島 健一 福岡大学, 薬学部, 教授 (00320309)
• Co-Investigator(Renkei-kenkyūsha): TAOKA Toshiaki 名古屋大学, 医学部, 准教授 (30305734) ; ABE Kohji 大阪大学, 医学部, 特任准教授 (80571207) ; NAKASE Hiroyuki 奈良県立医科大学, 医学部, 教授 (10217739)
• Research Collaborator: MUROI Carl, Izumi ; FUJIMURA Yoshihiro ; TSUBOI Akio
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: ADAMTS13 / クモ膜下出血 / 脳虚血 / 脳動脈瘤 / 血栓 / 炎症 / VWF / MRI

Outline of Final Research Achievements

ADAMTS13 cleaves VWF and reduces its prothrombotic and proinflammatory functions. Thus, ADAMTS13 protects the brain against acute ischemia by ameliorating post-ischemic brain hypoperfusion and inflammation. We studied the effect of ADAMTS13 on delayed cerebral ischemia after aneurysmal SAH. We evaluated the mice SAH model with 7.0 Tesla MRI and histology. The effects of ADAMTS13 on delayed cerebral microthrombi, cerebral vasospasm, neuronal inflammation, and neuronal death in the cerebral cortex and hippocampus were analyzed over time after SAH by comparing the groups with and without ADAMTS13 administration. ADAMTS13 significantly reduced microthrombosis, neuroinflammation and degenerative neurons, and improved neurological performance in SAH models. Our study with ADAMTS13 knockout mice signified neuroprotective effects of ADAMTS13 in SAH models. ADAMTS13 could provide a novel therapeutic approach for delayed cerebral ischemia after SAH as well as for acute ischemic stroke.

Free Research Field

脳神経外科、脳卒中、救急医学