Development of a treatment for cerebral microcirculation disorder in early brain injury (EBI) after subarachnoid hemorrhage

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19993
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Hirosaki University
• Principal Investigator: Naraoka Masato 弘前大学, 医学部附属病院, 講師 (10455751)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: くも膜下出血 / 脳微小循環障害 / 脳血管攣縮 / 遅発性脳虚血

Outline of Final Research Achievements

A subarachnoid hemorrhage model with rat internal carotid artery perforation was used; SD male rats (400-450 g) were used. Cerebral pressure is continuously monitored before the creation of the subarachnoid hemorrhage. For the rat subarachnoid hemorrhage model, cilostazol, veraprost sodium, and ozagrel sodium groups were created as treatment intervention groups. The cilostazol group showed significant inhibition of cerebral vasospasm and eNOS reduction, inhibition of neuronal apoptosis, and amelioration of microcirculatory disturbances by reducing cerebral edema, while the veraprost sodium and ozagrel sodium groups showed no significant difference.
In view of these results, we decided not to create a duplicate treatment group with cilostazol and investigated the use of apple polyphenol, which has been demonstrated to inhibit oxidative stress, as an additional therapeutic agent, and confirmed the improvement effect of eNOS.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

くも膜下出血は未だに多くの有病率、高い死亡率を伴う出血性脳卒中であり、開頭脳動脈瘤頚部クリッピング術やコイル塞栓術にて脳動脈瘤の根治治療にて一命を取り留めたとしても、その後の脳血管攣縮、遅発性脳虚血などによって重大な後遺症を残す可能性がある。後遺症の克服のため、遅発性脳虚血の原因の一つである脳微小循環障害の治療を目的とした研究を行い、シロスタゾールおよびポリフェノールにて改善の兆しが認められた。