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Open AccessCommunication

Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier

1
Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA
2
Department of Pharmaceutical Science, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
3
Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
4
Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA
*
Authors to whom correspondence should be addressed.
Equal contribution by authors.
Equal contribution by senior authors.
Sci. Pharm. 2020, 88(3), 40; https://doi.org/10.3390/scipharm88030040
Received: 13 August 2020 / Revised: 11 September 2020 / Accepted: 11 September 2020 / Published: 21 September 2020
Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood-brain barrier (BBB) permeability. It is widely used for the treatment of cluster headaches in Europe and is well tolerated in humans. The therapeutic potential for SPG stimulation in other central nervous system (CNS) diseases has yet to be explored. Glioblastoma Multiforme (GBM) remains one of the most difficult primary CNS neoplasms to treat, with an average survival of approximately 18 months at the time of diagnosis. Since 2004, the gold standard of treatment for GBM in the United States includes surgery followed by treatment with temozolomide (TMZ) and radiation. We sought to determine if SPG 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 BBB and reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. All the measurements 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 treatment paradigm shows novel delivery route by which we could more effectively and safely deliver TMZ in a targeted manner, to minimize systemic toxicity and maximize action at the target tissue. View Full-Text
Keywords: sphenopalatine ganglion (SPG) stimulation; liquid chromatography mass spectrometry (LCMS); temozolomide (TMZ); blood brain barrier (BBB) penetration sphenopalatine ganglion (SPG) stimulation; liquid chromatography mass spectrometry (LCMS); temozolomide (TMZ); blood brain barrier (BBB) penetration
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Theofanis, T.N.; Rochani, A.K.; Schmidt, R.F.; Lang, M.J.; Stricsek, G.P.; Rosenwasser, R.H.; Sharan, A.D.; Kaushal, G.; Iacovitti, L. Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier. Sci. Pharm. 2020, 88, 40.

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