Document Type


Publication Date



This article is the author’s final published version in Scientia Pharmaceutica, Volume 88, Issue 3, September 2020, Article number 0040.

The published version is available at Copyright © Theofanis et al.


Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood-brainbarrier (BBB) permeability. It is widely used for the treatment of cluster headaches in Europe and iswell tolerated in humans. The therapeutic potential for SPG stimulation in other central nervoussystem (CNS) diseases has yet to be explored. Glioblastoma Multiforme (GBM) remains one of themost difficult primary CNS neoplasms to treat, with an average survival of approximately 18 months atthe time of diagnosis. Since 2004, the gold standard of treatment for GBM in the United States includessurgery followed by treatment with temozolomide (TMZ) and radiation. We sought to determine ifSPG stimulation could increase chemotherapy concentrations in rodent brains with an intact BBB.Here, we show a statistically significant (p=0.0006), five-fold upregulation of TMZ crossing the BBBand reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. All themeasurements were performed using a highly sensitive liquid chromatography mass spectrometry(LCMS) method that was developed for quantitation of TMZ in plasma and brain tissue. Our treatmentparadigm shows novel delivery route by which we could more effectively and safely deliver TMZ ina targeted manner, to minimize systemic toxicity and maximize action at the target tissue.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.