Table 4.

Drugs/Agents targeting TRPV channels in modulating BBB integrity.

Drug/Agent	Dose	Route	Species	Model	Effect on BBB Integrity	Effect on TRPV Channels	Studies
Capsaicin	100 μM	ex-vivo	rat	Naive	Increase the permeability	TRPV1 Agonist	Hu et al. [62]
Capsazepine	1 μmol/kg	IP	rat	Experimental cerebral ischemia–reperfusion by middle cerebral artery occlusion (MCAO)	Reduced the permeability increase in brain capillaries induced by MCAO surgery	TRPV1 Antagonist	Hu et al. [62]
Capsazepine	35 nmol/L	Intra-cerebroventricular (ICV) injection	rat	Cerebral edema	Reduced the cerebral edema	TRPV1 Antagonist	Cernak et al. [98]
Capsazepine	1 μmol/kg	IP	rat	Experimental cerebral ischemia–reperfusion (MCAO)	Protect the BBB by limiting post-ischemic permeability increase	TRPV1 Antagonist	Gauden et al. [99]
Capsazepine	0.5, 1, 5, 10 mΜ	In vitro assay, in culture media	mouse	In vitro bEnd.3 cell line under stretch injury simulating traumatic brain injury (TBI)	Reduced the loss of ZO-1 induced by stretch injury in bEnd.3 cells	TRPV1 Antagonist	Yang et al. [93]
Capsazepine	1 μmol/kg, twice daily	IP	rat	TBI	Decreased the vasogenic brain edema and BBB disruption (Evans Blue extravasation), and preserved tight-junctions (TJ) upon brain injury	TRPV1 Antagonist	Yang et al. [65]
Cannabidiol	1 μM	In vitro assay, in culture media	human	In vitro BBB transwell model using primary brain microvascular endothelial cells (PBMECs)	Increased the TEER value of hPBMEC monolayers cultured in transwell	TRPV2 Agonist	Luo et al. [45]
Cannabidiol	10 μM	In vitro assay, in culture media	human	In vitro BBB model consisting by human PBMECs under oxygen-glucose deprivation (OGD) simulating ischemic stroke	Prevented the increase in BBB permeability induced by OGD	TRPV2 Agonist	Hind et al. [100]
GSK1016790A	50 pmol per rat	ICV injection	rat	Naive	Induced adherens and TJ protein degradation	TRPV4 Agonist	Zhao et al. [101]
4α-PDD	100 nM	In vitro assay, in culture media	mouse	In vitro BBB transwell model using bEnd3 cell monolayers	Increased the permeability of bEnd3 cell monolayers cultured in transwell	TRPV4 Agonist	Brown et al. [63]
4α-PDD	0.1 mg/kg	IV injection	rat	Experimental cerebral ischemia–reperfusion (MCAO)	Caused a 3.4-fold increase in microvessel density in the ischemic region in rats bearing MCAO surgery	TRPV4 Agonist	Chen et al. [102]
HC-067047	5, 50, 150 pmol per rat	ICV injection	rat	Autologous arterial blood was injected into the basal ganglia area to mimic ICH	Preserved the expression of adherens and tight junction (TJ) protein, as well as BBB integrity (Evans Blue extravasation) during ICH	TRPV4 Antagonist	Zhao et al. [101]
HC-067047	10 μmol per mouse	ICV injection	mouse	Experimental cerebral ischemia–reperfusion (MCAO)	Reversed BBB disruption and inhibited brain edema and infarction after MCAO surgery	TRPV4 Antagonist	Jie et al. [103]
HC-067047	50 pmol per rat	ICV injection	rat	Experimental cerebral ischemia–reperfusion (MCAO)	Reduced the BBB permeability increase induced by MCAO surgery	TRPV4 Antagonist	Xie et al. [104]