Table 1 MicroRNA candidates which are reported being involved in BBB disruption
miRNA | Disease model | Species | miRNA Expression | BBB dysfunction | Mechanism |
|---|---|---|---|---|---|
miR-107 [160] | Alzheimer's disease | In vitro human brain ECs(HBMEC) | Decreased | amyloid-β incubation down-regulates the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 | Overexpression protects BBB Via its direct target endophilin-1 |
miR-126-3P [161] | Intracerebral hemorrhage | Rat | Decreased | Cerebral edema, BBB leakage | Administration of miR-126 protects BBB via targeting PIK3R2 and the Akt signaling pathway |
miR-126-3P, 5P [162] | Stroke | Mice | Decreased | Brain edema, BBB leakage, decreased ZO-1 and Occludin | miR-126-3p, 5p overexpression reduced the expression of proinflammatory cytokines IL-1β and TNF-α and adhesion molecules VCAM-1 and E-selectin and attenuated BBB disruption |
miR-1303 [163] | Coxsackievirus A16 (CA16) infection model | In vitro and Monkey | Decrease | Degradation of junctional complexes Claudin4, Claudin5, CDH5, and ZO-1 | Infection downregulates miR-1303, which directly targets MMP9 |
miR-130a [164] | Stroke | Rat | Increase | Brain edema, BBB leakage | Increased miR-130a expression after stroke directly inhibit Homeobox A5 expression, which down-regulates occludin |
miR-132 [165] | Stroke | Mice | Decreased | Brain edema, BBB leakage | miR-132 overexpression decreased the degradation of tight junction proteins CDH5 and β-Catenin via targeting MMP9 |
miR-132 [166] | Stroke | Mice | Increased | Brain edema, BBB leakage, decreased expression of CDH5 and β-catenin | Targets MMP-9 and suppress the expression |
miR-143 [167] | methamphetamine-induced BBB dysfunction model | Mice/in vitro HBMEC | Increased | The decreased expression of TJ proteins including Claudin-5, ZO-1, and Occludin | miR-143 targets p53 upregulated modulator of apoptosis (PUMA) to induce BBB dysfunction |
miR-149-5p [168] | Stroke | Mice | Decreased | BBB leakage, Pericyte migration | Targeting sphingosine-1-phosphate receptor (S1PR)2 expressed in pericytes |
miR-150 [169] | Stroke | Rat | Increased | BBB leakage and decreased claudin-5 expression | miR-150 could regulate the claudin-5 expression and endothelial cell survival by targeting Tie-2 |
miR-155 [170] | Experimental autoimmune encephalomyelitis (EAE) | Mice/ in vitro HBMEC | Decrease | BBB leakage | Negative regulator of BBB targeting cell adhesion components annexin-2 and claudin-1 and focal adhesion components DOCK-1 and syntenin-1 |
miR-21 [171] | Stroke | Rat | Increase | Brain edema, BBB leakage | Target MAPK signaling |
miR-210 [172] | neonatal hypoxic-ischemic encephalopathy | Rat | Increased | cerebral edema, BBB leakage, reduced expression of tight junction protein occludin and adherens junction protein β-catenin | Increased level of miR-210 in the model negatively regulates BBB integrity |
MiR-212/132 [173] | Hypoxia | Mice/ in vitro HBMEC | increased | Increased expression of MiR-212/132 in hypoxic HBMEC decreased mRNA and protein expression of Cldn1, Jam3, and Tjap1 | By targeting Cldn1, Jam3, and Tjap1 |
miR-29b [174] | Stroke | Mice | Decrease | BBB leakage, Decreased expression of ZO-1, and occludin | Via targeting AQP4 |
miR29b [68] | BBB dysfunction model | Mice/in vitro | increased | Homocysteine induced BBB leakage | miR29b-mediate BBB dysfunction via targeting DNMT3b and MMP9 |
miR-501-3p [175] | Vascular dementia | Mice | Increase | Decreased expression of claudin-5, ZO-1, and occludin | TNFα upregulates the miR-501-3p that directly targets ZO-1 |
miR-539 [176] | Stroke | Rat | Decrease | BBB leakage | miR-539 targets MMP-9 |
miR-98 [177] | Stroke | Mice | Decrease | BBB leakage, | Reduced leukocytes infiltration and diminished microglia activation |
miRNA‐9‐5p [178] | TBI | Rat/In vitro | Increased | Decreased expression of claudin-5, ZO-1, and occludin | Via activating Hedgehog pathway and inhibiting NF‐κB/MMP‐9 pathway |