Table 4.

Non-coding RNAs mediate BBB regulatory effects of pharmaceutical drugs in CNS disorders

Year	pharmaceutical drugs	Non-coding RNAs	Levels change by agents	CNS Diseases	Study materials	Main regulatory effects on BBB	Main mechanisms	Refs.
2016	Methamphetamine	miR-143	Increased	Methamphetamine abuse	mice, hBMECs	Methamphetamine administration causes BBB damage. Silencing miR-143 ameliorates the increased BBB permeability induced by methamphetamine	Methamphetamine induces expression of miR-143 via sigma-1 receptor/MAPK (mitogen-activated protein kinase)/STAT3 pathway, and miR-143 regulates the EC permeability of endothelial cells via PUMA/NF-κB and p53/TJ proteins axis	[211]
2016	Salvianolic acid A	miR-101	Increased	SCI	rats, rBMECs	Sal A improves the recovery of neurological function after SCI	Sal A repairs BSCB integrity by the miR-101/Cul3/Nrf2/HO-1/ZO-1, occludin, and p-caveolin-1 signaling pathway	[212]
2018	Hydrogen gas (H2)	miR-21	Increased	TBI	rats	H2 treatment improves neurological dysfunction, alleviates brain edema, decreases lesion volume and BBB permeability	H2 treatment decreases the levels of oxidative products and increases the activities of endogenous antioxidant enzymes by upregulating miR-21 expression	[213]
2019	Memantine (MEM)	LINC00094	Decreased	AD	hCMEC/D3	MEM been used widely for AD therapy, and silencing LINC00094 enhances the effect of MEM on decreasing BBB permeability in AD microenvironment	Reduction of LINC00094 inhibits endophilin‐1 expression by upregulating miR‐224‐4p/miR‐497‐5p and promotes the expression of ZO‐1, occludin, and claudin‐5 in AD conditions	[214]
2019	Monomethyl fumarate (MF)	miR-139	Increased	Intracerebral hemorrhage	rats, SH-SY5Y	MF pretreatment markedly alleviates BBB disruption and brain edema	MF protects ICH in rats by inhibiting oxidative stress (increased Nrf2) and inflammatory response (decreased NF-κB) through activating the microRNA-139/Nrf2 axis	[215]
2019	Polydatin (PD)	Malat1	Increased	Ischemic stroke	rats, rBMECs	PD reduces cell toxicity and apoptosis, reduces inflammatory factors, and enhances the expression of BBB markers after OGD. PD reduces cerebral infarct volume and brain inflammation, protects cerebrovascular endothelial cells and BBB integrity after cerebral ischemia	PD activates the MALAT1/CREB (cAMP-response element binding protein)/PGC-1α (Peroxisome proliferator-activated receptor-gamma coactivator-1alpha)/PPARγ signaling pathway to protect endothelial cells against ischemia	[209]
2021	Alisol A 24-acetate (AA)	miR-92a-3p	Decreased	Ischemic stroke	BMECs	AA enhances cell viability and increases ZO-1, claudin-5, and occludin expression in OGD-insulted BMECs	AA protects against BMECs damage and TJ proteins loss through the inhibition of miR-92a-3p expression	[210]