BDNF Mediates Neuroprotection against Oxygen-Glucose Deprivation by the Cardiac Glycoside Oleandrin

• DOI: 10.1523/jneurosci.2700-13.2014
• Publication Date: 2014-01-15T18:11:24Z
• Authors: Michael J. Van Ka...; Dong Ning He; Denise E. Dunn; Peiying Yang; Robert A. Newman; Anne E. West; Donald C. Lo
• Keywords: Male; 0303 health sciences; Plant Extracts; Brain-Derived Neurotrophic Factor; Brain; Antioxidants; Rats; Oxygen; Rats, Sprague-Dawley; Cardenolides; 03 medical and health sciences; Glucose; Neuroprotective Agents; Organ Culture Techniques; Oxygen Consumption; Animals, Newborn; Animals; Female; Nerium

We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2extract ofNerium oleander, provides neuroprotection in bothin vitroandin vivobrain 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.