Calcium Signaling at the Blood–Brain Barrier in Stroke

TRPV4 promotes acoustic wave-mediated BBB opening via Ca2+/PKC-δ pathway

“…Previous studies have found calcium signaling to be involved in BBB disruption. Calcium influx can trigger a number of calcium-sensitive signaling cascades that alter the integrity of tight junctions [13] , [36] . Furthermore, Calcium homeostasis has been shown to mediate tight junction permeability [37] , [38] .…”

“…Calcium-mediated pathways, such as PKC pathway, have been reported to regulate epithelial tight junction integrity [11] , [12] , [13] , [14] . For example, ischemia induces calcium influx into brain endothelial cells [13] , which activates members of the PKC family and then induces various cellular mechanisms such as apoptosis and the loss of tight junction interactions, thus perturbing BBB integrity [13] , [14] , [15] . In contrast, prevention of BBB disruption can be achieved by calcium chelators [16] .…”

“…The channel is characterized by multimodal activation properties such as osmolarity, temperature and acidity [22] , [23] , [24] , [25] . Recent evidence demonstrates that the channel can also be activated by mechanical stress, and may have a crucial role in the modulation of BBB integrity [13] , [21] , [26] . Blockage of TRPV4 activity was found to potentially ameliorate brain injury in a variety of central nervous system disorders such as ischemic stroke [25] , [27] , [28] , intracerebral hemorrhage (ICH) [20] and traumatic brain injury (TBI) [29] , possibly through modulating BBB permeability and thus decreased edema.…”

Mechanobiological modulation of blood–brain barrier permeability by laser stimulation of endothelial-targeted nanoparticles

“…17 For example, activating Ca 2+ -sensitive signaling can increase BBB permeability by several pathways, including ERK1/2 phosphorylation and the resulting activation of actomyosin filament contraction. 18 Therefore, elucidating the relevant mechanobiological signaling pathways would help clarify the mechanism for OptoBBB and guide future clinical translation.…”

Calcium-Mediated Modulation of Blood-Brain Barrier Permeability by Laser Stimulation of Endothelial-Targeted Nanoparticles

“…Ca 2+ , as a second messenger, plays a crucial role in the signaling pathways that regulate endothelial permeability 13 . Activating Ca 2+ -sensitive signaling has been shown to increase BBB permeability by several pathways, including ERK1/2 phosphorylation-triggered activation of actomyosin filament contraction 14 . Elucidating the contribution of Ca 2+ and associated signaling would help clarify the mechanism for OptoBBB, which would provide additional insight into reversibly regulating vascular permeability through nanoscale mechanical and thermal perturbation.…”