Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier
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)...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | https://www.mdpi.com/2218-0532/88/3/40 |
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| author | Thana N. Theofanis Ankit K. Rochani Richard F. Schmidt Michael J. Lang Geoffrey P. Stricsek Robert H. Rosenwasser Ashwini D. Sharan Gagan Kaushal Lorraine Iacovitti |
| author_facet | Thana N. Theofanis Ankit K. Rochani Richard F. Schmidt Michael J. Lang Geoffrey P. Stricsek Robert H. Rosenwasser Ashwini D. Sharan Gagan Kaushal Lorraine Iacovitti |
| author_sort | Thana N. Theofanis |
| collection | DOAJ |
| description | 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-10T16:11:46Z |
| format | Article |
| id | doaj.art-9c1fb47fd29b4e1d85f59150d4136a3b |
| institution | Directory Open Access Journal |
| issn | 0036-8709 2218-0532 |
| language | English |
| last_indexed | 2024-03-10T16:11:46Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Scientia Pharmaceutica |
| spelling | doaj.art-9c1fb47fd29b4e1d85f59150d4136a3b2023-11-20T14:26:56ZengMDPI AGScientia Pharmaceutica0036-87092218-05322020-09-018834010.3390/scipharm88030040Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain BarrierThana N. Theofanis0Ankit K. Rochani1Richard F. Schmidt2Michael J. Lang3Geoffrey P. Stricsek4Robert H. Rosenwasser5Ashwini D. Sharan6Gagan Kaushal7Lorraine Iacovitti8Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pharmaceutical Science, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurosurgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pharmaceutical Science, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USASphenopalatine 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 (<i>p</i> = 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.https://www.mdpi.com/2218-0532/88/3/40sphenopalatine ganglion (SPG) stimulationliquid chromatography mass spectrometry (LCMS)temozolomide (TMZ)blood brain barrier (BBB) penetration |
| spellingShingle | Thana N. Theofanis Ankit K. Rochani Richard F. Schmidt Michael J. Lang Geoffrey P. Stricsek Robert H. Rosenwasser Ashwini D. Sharan Gagan Kaushal Lorraine Iacovitti Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier Scientia Pharmaceutica sphenopalatine ganglion (SPG) stimulation liquid chromatography mass spectrometry (LCMS) temozolomide (TMZ) blood brain barrier (BBB) penetration |
| title | Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier |
| title_full | Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier |
| title_fullStr | Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier |
| title_full_unstemmed | Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier |
| title_short | Sphenopalatine Ganglion Stimulation Upregulates Transport of Temozolomide across the Blood-Brain Barrier |
| title_sort | sphenopalatine ganglion stimulation upregulates transport of temozolomide across the blood brain barrier |
| topic | sphenopalatine ganglion (SPG) stimulation liquid chromatography mass spectrometry (LCMS) temozolomide (TMZ) blood brain barrier (BBB) penetration |
| url | https://www.mdpi.com/2218-0532/88/3/40 |
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