Sphenopalatine Ganglion Stimulation Upregulates Transport of Intra-Arterial Temozolomide Across the Blood–Brain Barrier. (1st September 2019)

• Record Type: Journal Article
• Authors: Theofanis, Thana N; Rochani, Ankit; Schmidt, Richard F; Lang, Michael J; Stricsek, Geoffrey; Kaushal, Gagan; Iacovitti, Lorraine; Sharan, Ashwini D; Rosenwasser, Robert H
• Is Part Of: Neurosurgery. Volume 66(2010)Supplement 1
• Publication Date: 2019-09-01
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyz310_151
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood–brain barrier (BBB) permeability. At the present time, it is widely used for the treatment of cluster headaches in Europe and is well tolerated for this use in humans. METHODS: In a rat model, we assessed the permeability of intra-arterial temozolomide with and without sphenopalatine ganglion stimulation. We developed a high-performance liquid chromatography and mass spectrometry method to measure temozolomide in rat plasma and brain tissue, with caffeine as the internal standard. RESULTS: Here we show a statistically significant ( P = .0006), 5-fold upregulation of TMZ crossing the BBB and reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. CONCLUSION: Glioblastoma multiforme (GBM) remains an extremely difficult disease to treat. Since 2004, the gold standard of treatment for GBM in the United States includes surgery + TMZ and radiation. Our treatment paradigm shows a mechanism in which we could more effectively and safely deliver TMZ in a targeted manner, to minimize systemic toxicity and maximize action at the target tissue. The SPG Stimulation treatment paradigm could be used in a broad spectrum of central nervous system (CNS) pathologies.