Blood-brain barrier opened by stimulation of the parasympathetic sphenopalatine ganglion: A new method for macromolecule delivery to the brain

David Yarnitsky, Yossi Gross, Adi Lorian, Alon Shalev, Itschak Lamensdorf, Rinat Bornstein, Shy Shorer, Avraham Mayevsky, Kaushik P. Patel, N. Joan Abbott, William G. Mayhan

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)303-309
Number of pages7
JournalJournal of neurosurgery
Volume101
Issue number2
DOIs
StatePublished - Aug 2004

Keywords

  • Blood-brain barrier
  • Electrical stimulation
  • Parasympathetic nervous system
  • Rat
  • Sphenopalatine ganglion

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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