Development of novel treatment using PDGF nanoparticles for cerebral infarction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09350
• 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: Kyushu University
• Principal Investigator: Arimura Koichi 九州大学, 病院, 講師 (00638025)
• Co-Investigator(Kenkyū-buntansha): 村田 正治 九州大学, 先端医療オープンイノベーションセンター, 教授 (30304744)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳梗塞 / nanoparticle / PDGF / drug delivery

Outline of Final Research Achievements

When PDGF-BB-modified nanoparticles (PDGFB-NP) were administered to cultured pericytes, marked phosphorylation of Akt was observed compared to controls. When PDGFB-NP was administered to a mouse model of cerebral infarction, PDGFB-NP accumulated in and around the cerebral infarction lesion confirmed by MAP2 staining, and reduced the cerebral infarct volume. In the cylinder test, a significant improvement in motor function was observed in the PDGFB-NP treatment group. We investigated the mechanism and found that NT-3 expression was significantly increased in PDGFRβ-positive pericytes via Akt phosphorylation. Furthermore, PDGFB-NPs reduced apoptosis and promoted wound healing by astrocytes.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

脳卒中は我が国の死因の第4位、寝たきりの原因の第1位であり、超高齢社会を迎えるにあたりその対策は喫緊の課題である。脳梗塞の急性期治療は血栓溶解や血栓回収のtime windowを超過した患者に対する有効な治療はなく、新たな治療開発が望まれている。本研究によりdrug delivery systemを活用したnanoparticleによる新しい脳梗塞治療の可能性が見出された。