A study on novel therapeutic strategies for stroke using progesterone.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: Tanaka Motoki 愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 主任研究員 (90584673)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脳梗塞 / 神経ステロイド / 脳保護作用

Outline of Final Research Achievements

Stroke is a leading cause of death and disability in a large number of countries. Thrombolysis by tissue plasminogen activator is the most effective treatment currently available, while it has limitations such as a very narrow therapeutic time-window (4.5 h after symptom onset). The present study examined effects of the progesterone receptor agonist nestorone on permanent focal cerebral ischemia (pMCAO) in adult and old male rats. Nestorone was continuously administered by Alzet osmotic pumps, starting at 18 h after pMCAO. Nestorone-treated adult male rats showed marked improvements of functional and histological outcomes 30 days after pMCAO. The same administration way of nestorone provided comparable neuroprotective effects in old male rats. These results suggest that post-ischemic administration of nestorone exerts long-term neuroprotection with a wider therapeutic time-window against permanent focal cerebral ischemia in both adult and old male rats.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

組織プラスミノゲン活性化因子（tPA）による血栓溶解療法は現在最も有効な脳梗塞治療法であるが、発症4時間半を経過した患者には適応できず、また脳出血発症などの重篤な副作用をもつ。一方nestoroneは、MCAO18時間後の投与であっても有意な脳保護効果を示し、発症後数時間が勝負と言われる現在の脳梗塞治療における限界を打破する可能性を有している。加えてnestoroneは、避妊薬としてアメリカ食品医薬品局から既に認可を受けており、重篤な副作用の懸念も少ないと考えられる。以上より、nestoroneは臨床的に極めて実用性の高い新規脳梗塞治療薬となり得る。