Blood—brain barrier opened by stimulation of the parasympathetic sphenopalatine ganglion: a new method for macromolecule delivery to the brain
| Autor: | Yossi Gross, David Yarnitsky, N. Joan Abbott, Itschak Lamensdorf, Rinat Bornstein, William G. Mayhan, Adi Lorian, Shy Shorer, Avraham Mayevsky, Alon Shalev, Kaushik P. Patel |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Cell Membrane Permeability Sphenoid Sinus Macromolecular Substances Central nervous system Drug delivery to the brain Stimulation Pharmacology Blood–brain barrier Parasympathetic nervous system chemistry.chemical_compound Nerve Fibers Cerebellum medicine Animals Rats Wistar Evans Blue Cerebral Cortex Palate business.industry Brain Dextrans Ganglia Parasympathetic Electric Stimulation Electrodes Implanted Rats Ganglion medicine.anatomical_structure chemistry Blood-Brain Barrier Postganglionic Parasympathetic Fiber Injections Intravenous business Neuroscience Fluorescein-5-isothiocyanate Brain Stem |
| Zdroj: | Journal of Neurosurgery. 101:303-309 |
| ISSN: | 0022-3085 |
| Popis: | Object. Drug delivery across the blood—brain barrier remains a significant challenge. Based on earlier findings, the authors hypothesized that parasympathetic innervation of the brain vasculature could be used to augment drug delivery to the brain. Methods. Using a craniotomy—cerebrospinal fluid superfusate paradigm in rats with an intravenous injection of tracer the authors demonstrated that stimulation of the postganglionic parasympathetic fibers of the sphenopalatine ganglion (SPG) increased the concentration of fluorescein isothiocyanate—dextran (4–250 kD) in the superfusate by two- to sixfold. A histological examination indicated the presence of dextran in the parenchyma. In another experiment the amount of Evans blue dye in the brain following SPG activation was similarly significantly elevated. The chemotherapeutic agents anti-HER2 monoclonal antibody and etoposide were also delivered to the brain and reached therapeutic concentrations. Brain homeostasis was not disturbed by this procedure; a measurement of nicotinamide adenine dinucleotide reduction did not show a decrease in the tissue metabolic state and brain water content did not increase significantly. Conclusions. Sphenopalatine ganglion activation demonstrates a promising potential for clinical use in the delivery of small and large molecules to the brain. |
| Databáze: | OpenAIRE |
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