Table 4.
The summary of the mechanisms of miRNAs in cerebral ischemia.
| Author | miRNA | Models/diseases | Species/Cell source species | Pathway/target | Functions | Reference |
|---|---|---|---|---|---|---|
| Chen et al., 2021 | miR-155 | MCAO, OGD/R | Mus musculus | Regulate TLR4; decrease SOCS-1, Myd88; Activate NF-κB | MicroRNA-155 affects ischemic stroke cell injury through TLR4/MYD88 signaling pathway | (80) |
| Fan et al., 2018 | miR-377 | MCAO, OGD/R | Rattus norvegicus | Increase EGR2, VEGF | MiR-377 regulates inflammation and angiogenesis in rats after cerebral ischemic injury | (81) |
| Song et al., 2020 | miR-1202 | OGD/R | Homo sapiens | Inhibite TLR4/NF-κB signaling pathway | MiR-1202 exerts neuroprotective effect on OGD/R-induced HM cell inflammation by negatively regulating Rab1a involved in TLR4/NF-κB signaling pathway | (82) |
| Ge et al., 2016 | miR-21-5p | In vitro scratch injury of microvascular endothelial cells | Rattus norvegicus | Regulate NF-κB signaling | miR-21-5p attenuates leakage of damaged brain microvascular endothelial barrier in vitro by inhibiting inflammation and apoptosis | (83) |
| Zhao et al., 2019 | miR-20b | – | Homo sapiens | Regulate NLRP3 signaling pathway, increase IL-1β, IL-18 | The miRNA-20b/NLRP3 axis may be a putative therapeutic target for cerebral ischemia. | (84) |
| Liu et al., 2015 | miR-124 | IS | Homo sapiens | Decrease CRP | Circulating miR-145 is associated with plasma hs-CRP in patients with acute ischemic stroke | (85) |
| Yang et al., 2015 | miR-203 | OGD/R | Mus musculus | Inhibite NF-κB signaling | miR-203 represents a novel target for regulating neuroinflammation and brain injury. | (86) |
| Tian et al., 2017 | miR-93 | MCAO/R | Mus musculus | Regulate Irak4 signaling | MiR-93 inhibits inflammation and apoptosis after cerebral ischemia-reperfusion by targeting IL-1 receptor-related kinase 4 | (87) |
| Xie et al., 2017 | miR-145-5p | MCAO/R | Rattus norvegicus | Regulate TNF-α | Interrupting miR-145-5p-Nurr1-TNF-α axis signaling in the acute phase may be an effective therapeutic strategy to alleviate neuronal injury during ischemia/reperfusion in rats. | (88) |
| Li et al., 2018b | miR-424 | IS | Homo sapiens | Increase TNF-α, IGF-1 | miR-424 prevents experimental stroke by inhibiting proliferation of microglia and activation of targeted cyclins. | (89) |
| Yin et al., 2017 | miR-181c | – | Homo sapiens | Decrease TLR4 | MiR-181c negatively regulates inflammatory responses in oxygen-glucose deprived microglia by targeting Toll-like receptor 4. | (90) |
| Mao et al., 2020 | miR-195 | OGD/R | Homo sapiens | Inhibite NF-κB signaling | MiR-195 attenuates oxygen-glucose deprivation/reperfusion-induced apoptosis by inhibiting IKKα-mediated NF-κB pathway | (91) |
| Xiang et al., 2019 | miR-183 | MCAO/R | Rattus norvegicus | Decrease IL-1β, IL-6 and TNF-α | miR-183 inhibits microglia activation and inflammatory factor expression in rats with cerebral ischemia-reperfusion through NF-κB signaling pathway | (92) |
| Wang 2018 | miR-210 | AIS | Homo sapiens | Increase IL-1β, IL-6, TNF-α, CCL2, CCL3 | Inhibition of miR-210 suppresses pro-inflammatory responses and reduces acute brain injury from ischemic stroke in mice | (93) |
| Li et al. 2020b | miR-26b | MCAO/R | Mus musculus | Inhibite TLR signaling pathway | Exosome-carried miR-26b-5p regulates microglial M1 polarization after cerebral ischemia/reperfusion | (94) |
| Guo et al., 2021 | miR-542-3p | OGD, MCAO | Mus musculus | Decrease TLR4 | MSC-derived exosomal miR-542-3p prevents ischemia-induced glial inflammatory response by inhibiting TLR4 | (95) |
| Dong et al., 2019 | miR-22 | MCAO | Rattus norvegicus | target p38 MAPK pathway | MiR-22 reduces inflammation in ischemic stroke via the p38 MAPK pathway | (96) |
| Zhang et al. 2021 | miR-146a-5p | OGD, MCAO | Mus musculus | inhibit IRAK1/TRAF6 pathway | miR-146a-5p derived from hUMSC exosomes attenuates microglia-mediated neuroinflammation and neurological deficits after ischemic stroke | (97) |
| Huang et al., 2018 | miR-210 | MCAO | Mus musculus | Increase TNF-α, IL-1β, IL-6, CCL2 and CCL3 | Inhibition of miR-210 suppresses pro-inflammatory responses and reduces brain damage in the acute phase of ischemic stroke | (98) |
| Li et al. 2020 | miR-381-3p | MCAO | Mus musculus | Inhibite Cebpb and Map3k8 | miR-381-3p downregulates Map3k8 and Cebpb to prevent ischemic stroke | (99) |
| Zheng et al., 2020 | miR-421-3p | OGD, MCAO | Mus musculus | Target m6A Reader YTHDF | Prevention of inflammatory responses in cerebral ischemia/reperfusion injury by targeting m6A Reader YTHDF1 to inhibit p65 mRNA translation | (100) |
| Zhou et al., 2021 | miR-19a/b-3p | OGD, MCAO | Rattus norvegicus | Increase FoxO3, SPHK1, NF-κB p65, and reduce SIRT1 | miR-19a/b-3p promotes inflammatory responses during ischemia-reperfusion by targeting the SIRT1/FoxO3/SPHK1 axis. | (101) |
| Zhang et al., 2020 | miR-665-3p | OGD | Mus musculus | Target TRIM8 to inhibit NF-κB signaling | miR-665-3p upregulation protects microglia from OGD-induced apoptosis and inflammatory responses by targeting TRIM8 to inhibit NF-κB signaling | (102) |
| Huang et al., 2022 | miR-135b-5p | MCAO | Rattus norvegicus | Relieve neurological deficit and focal cerebral ischemia-reperfusion neuronal injury | Upregulation of miR-135b-5p reduces neuronal damage and inflammatory responses in PSCI by targeting NR3C2 | (103) |
| Bao et al., 2021 | miR-5787 | OGD | THP-1 cell line (from Homo sapiens) | Inhibite LPS/TLR4 | MiR-5787 attenuates macrophage-mediated inflammation in ischemic cerebral infarction by targeting TLR4/NF-κB | (104) |
| Liu et al., 2021 | miR-200b-5p | MCAO | Mus musculus | Target SIRT1 | Inhibition of miR-200b-5p improves neural function, reduces inflammation and neuronal apoptosis in MCAO mice | (105) |
| Shi et al., 2021 | miR-532-5p | OGD, MCAO | Rattus norvegicus | Target CXCL1 | MicroRNA-532-5p prevents cerebral ischemia-reperfusion injury by directly targeting CXCL1 | (106) |
| Ye et al., 2021 | miR-27-3p | MCAO | Rattus norvegicus | Target PPARγ | Serum exosomal microRNA-27-3p aggravates brain injury and inflammation in patients with acute cerebral infarction by targeting PPARγ | (107) |
| Tu et al., 2021 | miR-34c-5p | OGD, MCAO | Rattus norvegicus | Regulates NCOA1 expression to inhibit nuclear factor-κB (NF-κB) activity, inhibits Caspase-3 and Bax, and up-regulates Bcl-2 | miR-34c-5p may play an important role in cerebral ischemia/reperfusion injury through inflammatory and apoptotic signaling pathways | (108) |
| Shan et al., 2021 | miR-221 | MCAO | Mus musculus | Decreased expression of TNF-α, MCP-1, VCAM-1 and IL-6 CCL2 and CCL3 | miR-221 exerts neuroprotective effects in ischemic stroke by inhibiting pro-inflammatory responses | (109) |
| Xie et al., 2020 | miR-874-3p | MCAO | Mus musculus | Decrease CXCL12, TNF-α, IL-1, IL-6, IL-8, and increase IL-10 | Up-regulation of microRNA-874-3p inhibits CXCL12 expression to promote angiogenesis and suppress inflammatory response in ischemic stroke | (110) |
| Deng et al., 2021 | miR-671-5p | OGD, MCAO | Mus musculus | Inhibit NF-κB expression | miR-671-5p may be a viable therapeutic target for reducing neuroinflammation in patients | (26) |
| Zha et al., 2021 | miR-153-5p | OGD, MCAO | Mus musculus | Targeting TLR4/p65/IkBa signaling pathway | Remote ischemic preconditioning partially reduces infarct volume and improves neurological function in acute ischemic stroke via miR-153-5p/TLR4/p65/IkBa signaling pathway | (111) |
| Liu et al., 2020 | miR-92b-3p | OGD, MCAO | Rattus norvegicus | Targeting TRAF3 in PC12 cells | miR-92b-3p attenuated OGD/R-induced apoptosis, mitochondrial dysfunction, and inflammatory responses by targeting TRAF3. | (112) |
| Yang et al., 2017 | miR-17-5p | MCAO | Mus musculus | Increase IL-6, MCP-1, VCAM1, TNF-α, decrease Bcl-2 and Bcl-w | Pharmacological inhibition of the miR-15a/16-1 cluster attenuates ischemic brain injury by upregulating anti-apoptotic proteins and inhibiting pro-inflammatory molecules. | (113) |
| Gamdzyk et al., 2020 | miR-17-5p | OGD, MCAO | Rattus norvegicus | Inhibit TXNIP/NLRP3 | PPAR-β/δ receptor agonist GW0742 activates miR-17-5p and inhibits TXNIP/NLRP3-mediated inflammation after hypoxic-ischemic injury in rat and PC12 cells | (114) |
| Tian et al., 2018 | miR-216a | OGD, MCAO | Mus musculus | Inhibits JAK2/STAT3 | Upregulation of miR-216a targeting JAK2 induces neuroprotection against ischemic injury in vitro and in vivo | (115) |
| Wang et al., 2018 | miR-182-5p | MCAO | Rattus norvegicus | Regulate TLR4 | MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting TLR4 | (116) |
| Zhao et al., 2020 | miR-223-3p | OGD, MCAO | Rattus norvegicus | Inhibit the expression of pro-inflammatory factors and promote the secretion of anti-inflammatory factors | Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia by inhibiting microglial M1 polarization-mediated inflammation | (117) |
| Yang et al., 2021 | miR-582-5p | OGD/R | PC12 cell line (from Rattus norvegicus) | Regulates cell viability, apoptosis, inflammation and oxidative stress | MiR-582-5p attenuates neonatal hypoxic-ischemic encephalopathy by targeting HMGB1 by inhibiting neuroinflammation and oxidative stress | (118) |
| Shi et al., 2020 | miR-217 | OGD, MCAO | Rattus norvegicus | Added IL-10 | MEF2D-HDAC5/ND6 signaling pathway regulated by miR-217 is involved in oxidative stress and inflammatory response after cerebral ischemia | (119) |
| Chen et al., 2020 | miR-193b-3p | OGD, MCAO | Rattus norvegicus | Regulates Leukotriene B4, Cysteinyl Leukotrienes and 5-LOX | MicroRNA-193b-3p attenuates focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression of 5-lipoxygenase | (120) |
| Zhou et al., 2020 | miR-199a | MCAO | Rattus norvegicus | promote inflammation | MiR-199a regulates autophagy and inflammation in rats with cerebral infarction by regulating mTOR expression | (121) |
| Fang et al., 2018 | miR-544 | OGD, MCAO | Mus musculus | Downregulation of IRAK4 expression | MicroRNA-544 inhibits inflammatory response and apoptosis after cerebral ischemia-reperfusion by targeting IRAK4 | (122) |
| Yu et al., 2020 | miR-199a-5p | OGD, MCAO | Rattus norvegicus | Inhibition of endoplasmic reticulum stress attenuates neuronal apoptosis and inflammation | HUVEC-derived miR-199a-5p inhibits ER stress-induced apoptosis and inflammation by targeting BIP. | (123) |
| Ni et al., 2015 | let-7c-5p | OGD | HUVECs (from Homo sapiens) | Inhibit microglial activation | The inhibition of microglial activation by let-7c-5p overexpression may be related to the protective effect of ischemic injury. | (124) |
| Song et al., 2020 | miR-1202 | MCAO, OGD/R | Mus musculus | Inhibit TLR4/NF-κB inflammatory signaling pathway | MiR-1202 exerts neuroprotective effects by negatively regulating its target protein Rab1a | (82) |
| Liu et al., 2022 | miR-665 | MCAO, OGD/R | Mus musculus | Targeting ROCK2 | MiR-665 participates in the protective effect of dexmedetomidine on ischemic stroke through ROCK2/NF-κB axis | (125) |
| Wang et al., 2020 | miR-139 | OGD/R | Human neuroblastoma cells SH-SY5Y (from Homo sapiens) | Inhibits pyroptosis and up-regulation of NLRP3, caspase-1, ASC, GSDMD Nterm, and release of IL-1β, IL-18 and LDH | Up-regulation of miR-139 exerts neuroprotection against OGD/R-induced nerve injury by negatively regulating c-Jun/NLRP3 inflammasome signaling. | (126) |
| Dong et al., 2016 | miR-1202 | OGD/R | Human microglial cells (from Homo sapiens) | Inhibit TLR4/NF-κB pathway | MiR-1202 exerts neuroprotective effect on OGD/R-induced HM cell inflammation by negatively regulating Rab1a involved in TLR4/NF-κB signaling pathway | (127) |
| Wu et al. 2020 | miR-124-5p | MCAO, OGD/R | Rattus norvegicus | Modulation of NOX2 significantly inhibits NF-κB signaling activation and production of TNFα and IL-6 | miR-124-5p/NOX2 Axis regulates ROS production and inflammatory microenvironment to prevent brain I/R injury | (128) |
| Ma et al., 2020 | miR-155 | MCAO | Mus musculus | Promotes M2 polarization of microglia | Resveratrol promotes M2 polarization of microglia and reduces neuroinflammation after cerebral ischemia by inhibiting miR-155 | (129) |
| Li et al., 2019 | miR-542-3p | MCAO | Mus musculus | Attenuated apoptosis, reactive oxygen species, and activation of inflammatory responses. | Adipose-derived mesenchymal stem cells alleviate ischemic brain injury in rats by regulating miR-21-3p/MAT2B signaling | (130) |
| Liu et al., 2016 | miR-9 | MCAO | Rattus norvegicus | Downregulate MCPIP1 | Electroacupuncture inhibits inflammatory injury after ischemic stroke by targeting miR-9-mediated NF-κB signaling pathway | (131) |
| Song et al., 2022 | miR-203-3p | MCAO | Rattus norvegicus | Inhibits neuronal apoptosis and inflammation | Sevoflurane protects mice from cerebral ischemic injury by modulating the microRNA-203-3p/HDAC4/Bcl-2 axis | (132) |
| Song et al., 2019 | miR-181c-3p | MCAO | Rattus norvegicus | Inhibit CXCL1 expression | Cortical neuron-derived exosomal microRNA-181c-3p inhibits neuroinflammation by downregulating CXCL1 in astrocytes in a rat model of ischemic brain injury | (133) |