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

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 incre...

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Published in:The Journal of neuroscience 2014-01, Vol.34 (3), p.963-968
Main Authors: Van Kanegan, Michael J, He, Dong Ning, Dunn, Denise E, Yang, Peiying, Newman, Robert A, West, Anne E, Lo, Donald C
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antioxidants - physiology
Brain - drug effects
Brain - metabolism
Brain-Derived Neurotrophic Factor - physiology
Cardenolides - pharmacology
Female
Glucose - deficiency
Male
Nerium
Nerium oleander
Neuroprotective Agents - pharmacology
Organ Culture Techniques
Oxygen - metabolism
Oxygen Consumption - physiology
Plant Extracts - pharmacology
Rats
Rats, Sprague-Dawley
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.2700-13.2014