BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.

Published

Journal Article

We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.

Full Text

Duke Authors

Cited Authors

  • Van Kanegan, MJ; He, DN; Dunn, DE; Yang, P; Newman, RA; West, AE; Lo, DC

Published Date

  • January 15, 2014

Published In

Volume / Issue

  • 34 / 3

Start / End Page

  • 963 - 968

PubMed ID

  • 24431454

Pubmed Central ID

  • 24431454

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.2700-13.2014

Language

  • eng

Conference Location

  • United States