Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs.
The blood-brain barrier (BBB) is a major obstacle for movement of large molecules to and from the brain. Stimulation of the sphenopalatine ganglion (SPG), the major source of parasympathetic innervation to brain vasculature, is known to vasodilate brain vessels, and has recently been shown to also increase the permeability of the BBB in the rat. In this work, we studied the effect of SPG stimulation on BBB permeability in larger animals--Beagle dogs. Left SPG was exposed by lateral approach in five Beagle dogs, and stimulated at 10 Hz. FITC labeled 10 kDa dextran was continuously infused to the left atrium during stimulation, and cerebral angiography was periodically obtained via the vertebral artery. Three control dogs received labeled dextran, without SPG exposure or stimulation. Brains were perfused with saline thoroughly at the end of stimulation, and samples from various regions were taken for fluorescence reading of tissue homogenates. Cerebral vasodilatation was evidenced in all but one dog, whose fluorescence results were consequently excluded from analysis, assuming that its SPG had been damaged by surgery. Fluorescence was significantly higher in the four stimulated compared to the three non-stimulated animals; e.g. mean FITC-dextran concentration in the anterior brain regions was 0.98+/-0.12 ug (mean+/-S.D.) FITC/g brain for experimental animals, and 0.40+/-0.02 for controls (p<0.01). No effect was seen in the pons and cerebellum (0.68+/-0.22 vs. 0.60+/-0.03, NS) whose vascular innervation is supplied by the otic rather than the SPG ganglion. SPG stimulation appears to be an effective way to increase BBB permeability, allowing introduction of large molecules to the brain. This could be a therapeutic method for a wide variety of brain disorders, including tumors and neurodegenerative diseases.
Department of Neurology, Rambam Medical Center, Technion Faculty of Medicine, Bat Galim, Haifa 31096, Israel. davidy@tx.technion.ac.il
David
D
Yarnitsky
Yossi
Y
Gross
Adi
A
Lorian
Alon
A
Shalev
Shy
S
Shorer
Toshiki
T
Tanaka
Kazuhide
K
Ayajiki
Mineko
M
Fujimiya
Tomio
T
Okamura
D000818:Animals; D001812:Blood-Brain Barrier / Q000294:innervation* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply*; D003911:Dextrans / Q000493:pharmacokinetics; D004285:Dogs; D004558:Electric Stimulation; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007839:Functional Laterality; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D010159:Palate; D010539:Permeability; D013101:Sphenoid Sinus; D013666:Tears / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D003911:Dextrans; D005456:Fluorescent Dyes; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate