Sphenopalatine ganglion stimulation is a reversible and frequency-dependent modulator of the blood-brain barrier.
Brain Res
; 1718: 231-241, 2019 09 01.
Article
em En
| MEDLINE
| ID: mdl-31034813
ABSTRACT
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 70â¯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 10â¯Hz maximally increased BBB permeability, exhibiting a 6-fold increase in fluorescent traceruptake (1.66% vs 0.28%, pâ¯<â¯0.0001). This effect was reversed 4-hours after stimulation (0.36% uptake, pâ¯=â¯0.99). High-frequency stimulation at 20â¯Hz and 200â¯Hz did not increase tracer extravasation, (0.26% and 0.28% uptake, pâ¯=â¯>0.999 and pâ¯=â¯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, pâ¯<â¯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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Fossa Pterigopalatina
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos