TABLE 3.
Therapeutic drug candidates for modulating BBB integrity.
| Therapeutic drug candidates | Species | Cocultured cells with BMECs | Experimental conditions | Cellular events in BMECs | References |
| Minocycline | Human | - | Oxygen deprivation | TEER ↑ Claudin-5 expression ↑ Occludin expression ↑ ZO-1 expression ↑ | Yang et al., 2015 |
| Alogliptin | Human | - | OGD/reoxygenation | Permeability (FITC-Dextran) ↓ Occludin expression ↑ ZO-1 expression ↑ | Hao et al., 2019 |
| Zafirlukast | Human | - | OGD/reoxygenation | Permeability (FITC-Dextran) ↓ Occludin expression ↑ ZO-1 expression ↑ | Zeng et al., 2020 |
| Siponimod | Human | Astrocytes | Physiological conditions | Permeability (FITC-Dextran) ↓ Claudin-5 expression ↑ ZO-1 expression ↑ | Spampinato et al., 2021 |
| Astrocytes | TNF-α and INF-γ treatment | PI3K/Akt signaling pathway↑ Permeability (FITC-Dextran) ↓ TEER ↑ Claudin-5 expression ↑ ZO-1 expression ↑ | Spampinato et al., 2021 | ||
| Memantine | Human | Pericytes and astrocytes | Amyloid-β1–42 treatment | LINC00094 expression ↓ Permeability (horseradish peroxidase) ↓ TEER ↑ Claudin-5 expression ↑ Occludin expression ↑ ZO-1 expression ↑ | Zhu et al., 2019 |
| Metformin | Rat | - | Physiological conditions | AMPK activation ↑ Permeability (sodium fluorescein) ↓ Permeability (Evans blue albumin) ↓ TEER ↑ | Takata et al., 2013 |
| Pitavastatin | Rat | - | Physiological conditions | Mevalonate pathway ↓ Permeability (sodium fluorescein) ↓ Permeability (Evans blue albumin) → TEER ↑ Claudin-5 expression ↑ | Morofuji et al., 2010 |
| Cilostazol | Rat | - | Physiological conditions | cAMP↑ Permeability (sodium fluorescein) ↓ TEER ↑ | Horai et al., 2013 |
| Rat | Pericytes and astrocytes | OGD/reoxygenation | TEER ↑ | Horai et al., 2013 | |
| Rat | Pericytes and astrocytes | TGF-β1 treatment | TEER ↑ | Takeshita et al., 2014 | |
| Rat | Pericytes and astrocytes | AGEs treatment under OGD/reoxygenation | TGF-β1 ↓ TEER ↑ Claudin-5 expression ↑ | Takeshita et al., 2014 | |
| Candesartan | Rat | Astrocytes | OGD/reoxygenation | Permeability (sodium fluorescein) ↓ TEER ↑ Improved localization of claudin-5 and occludin | So et al., 2015 |
| Perampanel | Rat | Astrocytes and neurons | Glutamate treatment | Permeability (sodium fluorescein) ↓ TEER ↑ | Chen et al., 2020 |
| Rat | Astrocytes and neurons | Traumatic neuronal injury model | Permeability (sodium fluorescein) ↓ TEER ↑ | Chen et al., 2020 | |
| Ruxolitinib | Rat | Pericytes | OSM treatment | Permeability (sodium fluorescein) ↓ TEER ↑ (JAK/STAT3 signaling pathway in pericytes ↓) | Takata et al., 2019 |
| Lithium | Mouse | - | OGD/reoxygenation | Wnt/β-catenin signaling pathway ↑ TEER ↑ | Ji et al., 2021 |
| Omarigliptin | Mouse | - | LPS treatment | Toll-like receptor 4/myeloid differentiation factor 88/NF-κB signaling pathway ↓ Permeability (FITC-Dextran) ↓ Claudin-1 expression ↑ Claudin-5 expression ↑ | Du and Wang, 2020 |
| Propofol | Mouse | Astrocytes and microglia | Oxygen deprivation | TEER ↑ (Heat shock protein (HSP) 32 expressions and nuclear translocation of nuclear factor-E2-related factor 2 in microglia ↑) (HSP27 expressions and nuclear translocation of heat shock factor 1 in astrocytes ↑) | Sun et al., 2019 |
| 5′-azacytidine | Mouse | - | Homocysteine treatment | miR-29b expression ↓ Permeability (FITC-albumin) ↓ | Kalani et al., 2014 |