Study of the pathogenesis of early brain injury after subarachnoid hemorrhage

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19962
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Mie University
• Principal Investigator: Fujimoto Masashi 三重大学, 医学部附属病院, 診療等従事者 (00437104)
• Research Collaborator: SUZUKI Hidenori ; YOSHIDA Toshimichi ; YOSHIDA Kyoko ; LIU Lei ; NISHIKAWA Hirofumi ; NAKANO Fumi ; NAKATSUKA Yoshinari
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: くも膜下出血 / 脳損傷 / アポトーシス / 炎症 / 細胞外マトリックス

Outline of Final Research Achievements

Tenascin-C (TNC), a matricellular protein, is upregulated in brain parenchyma after experimental subarachnoid hemorrhage (SAH). The aim of this study was to investigate effects of TNC knockout (TNKO) on neuronal apoptosis and neuroinflammation, both of which are important constituents of early brain injury (EBI) after SAH. C57BL/6 wild-type mice or TNKO mice underwent sham or filament perforation SAH modeling. Deficiency of TNC significantly alleviated post-SAH neurobehavioral impairments and neuronal apoptosis. The protective effects of TNKO on neurons were associated with the inhibition of a caspase-dependent apoptotic pathway, which was at least partly mediated by Toll-like receptor 4 /nuclear factor-κB /interleukins-1β and -6 signaling cascades. This study first provided the direct evidence that TNC causes post-SAH neuronal apoptosis and neuroinflammation, potentially leading to the development of a new molecular targeted therapy against EBI.

Free Research Field

脳血管障害