RT Journal Article
SR Electronic
T1 Protein Nanoparticles Modified with PDGF-B as a Novel Therapy After Acute Cerebral Infarction
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0098-21.2021
DO 10.1523/ENEURO.0098-21.2021
VO 8
IS 5
A1 Takagishi, Soh
A1 Arimura, Koichi
A1 Murata, Masaharu
A1 Iwaki, Katsuma
A1 Okuda, Tomohiro
A1 Ido, Keisuke
A1 Nishimura, Ataru
A1 Narahara, Sayoko
A1 Kawano, Takahito
A1 Iihara, Koji
YR 2021
UL http://www.eneuro.org/content/8/5/ENEURO.0098-21.2021.abstract
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.