PT - JOURNAL ARTICLE AU - Takagishi, Soh AU - Arimura, Koichi AU - Murata, Masaharu AU - Iwaki, Katsuma AU - Okuda, Tomohiro AU - Ido, Keisuke AU - Nishimura, Ataru AU - Narahara, Sayoko AU - Kawano, Takahito AU - Iihara, Koji TI - Protein Nanoparticles Modified with PDGF-B as a Novel Therapy After Acute Cerebral Infarction AID - 10.1523/ENEURO.0098-21.2021 DP - 2021 Sep 01 TA - eneuro PG - ENEURO.0098-21.2021 VI - 8 IP - 5 4099 - http://www.eneuro.org/content/8/5/ENEURO.0098-21.2021.short 4100 - http://www.eneuro.org/content/8/5/ENEURO.0098-21.2021.full SO - eNeuro2021 Sep 01; 8 AB - 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.