Protein nanoparticles modified with pdgf-b as a novel therapy after acute cerebral infarction

Soh Takagishi, Koichi Arimura, Masaharu Murata, Katsuma Iwaki, Tomohiro Okuda, Keisuke Ido, Ataru Nishimura, Sayoko Narahara, Takahito Kawano, Koji Iihara

Research output: Contribution to journalArticlepeer-review

Abstract

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 adminis-ter 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.

Original languageEnglish
Article numberENEURO.0098-21.2021
JournaleNeuro
Volume8
Issue number5
DOIs
Publication statusPublished - Sep 1 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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