Research Paper Volume 11, Issue 23 pp 11391—11415

Melatonin protects blood-brain barrier integrity and permeability by inhibiting matrix metalloproteinase-9 via the NOTCH3/NF-κB pathway

Figure 10. Schematic diagram of the regulatory effects of melatonin on BBB integrity and permeability. IL-1β induced NOTCH3 (NICD) expression which activated NF-κB/p65 expression. NF-κB/p65 translocated to the nucleus to induce MMP-9 expression, and MMP-9 disrupted BBB integrity and permeability. When melatonin, DAPT, PDTC, and SB-3CT were added respectively, NOTCH3 expression was significantly inhibited, leading to decreased NF-κB/p65 and MMP-9 expression, which protected BBB integrity and permeability.