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Updated: Jan 25, 2026
Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation
Published on: August 20, 2019
Sphenopalatine ganglion stimulation is a reversible and frequency-dependent modulator of the blood-brain barrier
Richard F Schmidt1, Thana N Theofanis1, Michael J Lang2
1Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
Background:
The sphenopalatine ganglion (SPG) is a vasoactive mediator of the anterior intracranial circulation in mammals. SPG stimulation has been demonstrated to alter blood-brain barrier (BBB) permeability, although this phenomenon is not well characterized.
Objective:
To determine the effect of SPG stimulation on the BBB using rat models.
Methods:
Extravasation of fluorescent tracer 70 kDa FITC-dextran into rat brain specimens was measured across a range of stimulation parameters to assess BBB permeability. Tight junction (TJ) morphology was compared by assessing differences in the staining of proteins occludin and ZO-1 and analyzing ultrastructural changes on transmission electron microscopy (TEM) between stimulated and unstimulated specimens.
Results:
SPG stimulation at 10 Hz maximally increased BBB permeability, exhibiting a 6-fold increase in fluorescent traceruptake (1.66% vs 0.28%, p < 0.0001). This effect was reversed 4-hours after stimulation (0.36% uptake, p = 0.99). High-frequency stimulation at 20 Hz and 200 Hz did not increase tracer extravasation, (0.26% and 0.28% uptake, p = >0.999 and p = 0.998, respectively). Stimulation was associated a significant decrease in the colocalization of occludin and ZO-1 with endothelial markers in stimulated brains compared to control (74.6% vs. 39.7% and 67.2% vs. 60.4% colocalization, respectively, p < 0.0001), and ultrastructural changes in TJ morphology associated with increased BBB permeability were observed on TEM.
Conclusion:
This study is the first to show a reversible, frequency-dependent increase in BBB permeability with SPG stimulation and introduces a putative mechanism of action through TJ disruption. Bypassing the BBB with SPG stimulation could enable new paradigms in delivering therapeutics to the CNS. Further study of this technology is needed.
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