期刊
ENEURO
卷 8, 期 5, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0098-21.2021
关键词
cerebral infarction; nanoparticle; neuroprotection; pericyte; platelet-derived growth factor PDGF-B
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan Japan Society for the Promotion of Science [18K16588, 18K12079, 19H04470]
- Bristol Myers Squibb Research grant
- Grants-in-Aid for Scientific Research [18K16588, 18K12079, 19H04470] Funding Source: KAKEN
PDGF-B modified HSPNPs showed therapeutic effects on cerebral infarction by significantly reducing infarct volumes, improving neurological function, promoting neurotrophin production, and reducing cell apoptosis.
Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs ( HSPNPs) to examine its therapeutic effect in cerebral infarction. PDGF-B modified HSPNPs (PDGF-B HSPNPs) were injected 1 d after transient middle cerebral artery occlusion (t-MCAO) in CB-17 model mice. We analyzed the infarct volume and motor functional recovery at 3 and 7 d. PDGF-B HSPNPs were specifically distributed in the infarct area, and compared with HSPNPs alone, they significantly reduced infarct volumes and improved neurologic function 3 and 7 d after administration. PDGF-B HSPNP administration was associated with strong phosphorylation of Akt in infarct areas and significantly increased neurotrophin (NT)-3 production as well as reduced cell apoptosis compared with HSPNPs alone. Moreover, astrogliosis in peri-infarct area was significantly upregulated with PDGF-B HSPNPs compared with HSPNPs alone. Treatment with PDGF-B HSPNPs might be a novel approach for treating cerebral infarction.
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