Neural Plasticity

Review Article

Function of Connexins in the Interaction between Glial and Vascular Cells in the Central Nervous System and Related Neurological Diseases

Table 1

Connexin inhibitors link to the BBB permeability in vitro.


Cell type	Stimulus	Treatment	Main outcome	Reference

Porcine BBB ECs		18β-Glycyrrhetinic acid and oleamide	Inhibits the barrier function of TJs and GJIC without morphological change	[12]
Mouse brain CCM3KD ECs		Gap27	Inhibits BBB hyperpermeability through blocking Cx43 GJs, restoring ZO-1 to TJ structures	[59]
Rat brain RBE4 cells	Bradykinin	Gap27, Cx37-siRNA, and Cx43-siRNA	Inhibits endothelial hyperpermeability through reducing intracellular calcium oscillations	[57]
Rat brain RBE4 cells	A reduction in extracellular Ca²⁺ concentration	Gap27	Inhibits endothelial hyperpermeability through blocking the intercellular Ca²⁺ waves and repressing PKC, CaMKII, and actomyosin contraction	[77]
Rat brain (RBE4, GP8 cells)	TNF-α	Gap26	No effect on the elevated baseline ATP release from rat brain endothelial cells treated by TNF-α	[82]
Rat brain GP8 cells		Gap26 and Gap27	Inhibits intracellular ATP release through blocking Cx43-HCs which contribute to the intercellular propagation of calcium signals	[81]
Organotypic hippocampal slices from 7-day-old Wistar rats	Albumin	Carbenoxolone, Gap27, and SLS peptide	In developing hippocampal networks, the generation and initiation of spontaneous recurrent seizure-like activity depend on the opening of glial GJs	[119]
Astrocytes from the cortex and spinal cord of the SCI mouse model	TNF-α	Gap26, Gap27, and Cx43-siRNA	TNF-α activated Cx43-HCs, rather than GJIC, to release CXCL1 which contribute to neuropathic pain	[94]
Astrocytes from cortex of Sprague-Dawley rat	Aβ-peptide	Octanol (an uncoupler of gap junctions)	Functional GJs are not required for calcium-wave propagation; they play a role in the enhancement of calcium waves induced by Aβ.	[110]

ECs: endothelial cells; SCI: spinal cord injury; TJs: tight junctions; GJs: gap junctions; ZO: zona occludin; PKC: protein kinase C; CaMKII: Ca²⁺/calmodulin-dependent kinase II; HCs: hemichannels; GJIC: gap junction intercellular communication; Aβ: amyloid β.