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] |