Introduction: Anatomical studies have shown that postganglionic parasympathetic nerve fibers originating from the sphenopalatine ganglion (SPG) innervate the anterior circulation in mammals.1,2 Previous studies suggest that stimulation of the SPG increases permeability of the blood-brain barrier (BBB).3,4 However, the reversibility of this phenomenon has not been demonstrated.
Methods: Female Sprague-Dawley rats weighing 230-240g underwent femoral vein injection of 1mL of 100mg/mL 70kDa Fluorescein-Isothiocyanate (FITC) conjugated dextran with or without SPG stimulation. Stimulation was performed at 10Hz and 5V, with cycles consisting of 90 seconds “on” followed by 60 seconds “off.” Stimulation included a 6-cycle priming period followed by 10 cycles with concurrent tracer injection. Rats were assigned to control (no surgery, n=5), stimulation (concurrent tracer injection, n=8) or delayed injection (tracer injection 4 hours after stimulation, n=5) groups. Following tracer injection, rats were sacrificed, blood was obtained via cardiac puncture, and animals were perfused with 50ml of heparinized saline. Subsequently, brains were harvested, sectioned into 5 specimens per hemisphere, and homogenized in 7.5% trichloric acid. Fluorescence was measured from the supernatant with excitation and emission wavelengths of 490nm and 520nm, respectively. Concentrations were obtained from internal standards, and uptake was measured as a percentage of serum fluorescence.
Results: Mean fluorescent uptake (±Standard error) in the control, stimulation and delay groups were 0.28%±0.02%, 1.6±0.12% and 0.26±0.02%, respectively. There was a significant difference between the stimulation group and both the control (p<0.001) and delay (p=0.002) groups. There was no difference between the control and delay groups (p=0.97).
Conclusions: This is the first study to assess the reversibility of blood-brain barrier opening from SPG stimulation. This provides valuable insight into its possible use as an adjunct for treatments targeting the brain, since stimulation does not appear to elicit any lasting effect on the BBB.
Patient Care: This provides additional support for the possible use of sphenopalatine ganglion stimulation as a therapeutic adjunct to the delivery of targeted therapies to the CNS. Reversible opening of the BBB may be able to enhance therapeutic delivery to the CNS without permanently altering the BBB.
Learning Objectives: 1) Sphenopalatine ganglion stimulation modulates permeability of the blood-brain barrier.
2) Stimulation at 10Hz increases uptake of fluorescent tracers into the brain parenchyma compared with controls.
3) This effect is reversible with cessation of stimulation for 4 hours.
References: 1. Hara H, Zhang QJ, Kuroyanagi T, Kobayashi S. Parasympathetic cerebrovascular innervation: An anterograde tracing from the sphenopalatine ganglion in the rat. Neurosurgery. 1993;32(5):822-827. doi:10.1227/00006123-199305000-00016
2. Suzuki N, Hardebo JE, Owman C. Origins and Pathways of Choline-Acetyltransferase Positive Parasympathetic Nerve-Fibers to Cerebral Vessels in Rat. J Cereb Blood Flow Metab. 1990;10(3):399-408.
3. Yarnitsky D, Gross Y, Lorian A, et al. Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs. Brain Res. 2004;1018(2):236-240. doi:10.1016/j.brainres.2004.05.103
4. Yarnitsky D, Gross Y, Lorian A, et al. Blood—brain barrier opened by stimulation of the parasympathetic sphenopalatine ganglion: a new method for macromolecule delivery to the brain. J Neurosurg. 2004;101(2):303-309. doi:10.3171/jns.2004.101.2.0303