Table 2.
Animal studies investigating the therapeutic efficacy of miRNA in the setting of ischaemic stroke
| Agent (Author) | Design | Key findings |
|---|---|---|
| miR-27b antagomir | Model: MCAO mice | Increased neuronal survival and promoted neurogenesis by directly regulating AMPK expression |
| (Wang et al. 2019) | Delivery strategy: NA | Improved functional outcome and spatial memory |
| Route: intravenous | ||
| Time of administration: day 7, 14 and 28 after MCAO | ||
| miR-107 antagomir | Model: MCAO rats | Suppressed VEGF mRNA and protein expression and promoted angiogenesis through directly binding to Dicer-1 |
| (Li et al.) | Delivery strategy: NA | Reduced infarct volume and improved capillaries in ischaemic boundary zone |
| Route: intraventricular | ||
| Time of administration: 1 h after MCAO | ||
| miR-126 agomir | Model: MCAO mice | Promoted vascular remodelling and neurogenesis |
| (Qu et al.) | Delivery strategy: lentiviral vector | Improved neurobehavioral recovery and reduced brain atrophy volume |
| Route: intracerebral | ||
| Time of administration: 7 days after MCAO | ||
| miR-126-Primed EPCs | Model: MCAO mice | Increased proliferation, migration and tubulogenic capacity of EPCs |
| (Pan et al.) | Delivery strategy: lentiviral vector | Decreased ROS and increased NO production of EPCs by activating PI3K/Akt/eNOS pathway |
| Route: intravenous | miR-126 augmented the therapeutic efficacy of EPCs and helped attenuate infarct volume and neurological deficits while improving cerebral blood flow, microvascular density and angiogenesis | |
| Time of administration: 2 h after MCAO | ||
| miR-126-3p or -5p agomir | Model: MCAO mouse | Reduced cerebral infarct and oedema volumes |
| (Pan et al.) | Delivery strategy: lentiviral vector | Improved zonula occludens-1 and occlusion expressions and maintained BBB function |
| Route: stereotactic injection | Reduced pro-inflammatory cytokine (IL-1β and TNF) and adhesion molecule (VCAM-1 and E-selectin) expressions | |
| Time of administration: 2 weeks before MCAO | ||
| miR-132 agomir | Model: MCAO mice | Suppressed MMP-9 expression and maintained tight junction VE-cadherin and β-catenin levels |
| (Zuo et al. 2019) | Route: intraventricular | Reduced infarct and oedema volumes, as well as neurological deficits |
| Delivery strategy: NA | ||
| Time of administration: 2 h before MCAO | ||
| miR-155 antagomir | Model: distal MCAO mouse | Improved blood flow and microvascular integrity and reduced neuronal damages in the peri-infarct area |
| (Caballero-Garrido et al.) | Delivery strategy: novel locked nucleic acid technology | Reduced infarct size and neurological impairments |
| Route: intravenous | Maintained the integrity of tight junctions through improved zonula occluden 1 protein | |
| Time of administration: 48 h after MCAO | Prevented post-ischaemic inflammation by decreasing cytokine and chemokine gene expressions | |
| miR-195 agomir | Model: MCAO rats | Decreased inflammatory response and neuronal cell death via direct suppression of NF-κB and Sema3A/Cdc42/JNK signalling pathways |
| (Cheng et al.) | Delivery strategy: lentiviral vector | Stimulated proliferation and mobilisation of neural stem cells toward infarct area |
| Route: intravenous | Improved neurological function and reduced infarct size | |
| Time of administration: 6 h after MCAO | ||
| miR-195 agomir | Model: MCAO rats | Reduced neuronal cell death by downregulating KLF-5 and JNK expressions |
| (Chang et al. 2020) | Delivery strategy: rAAV2/EGFP vector | Decreased infarct volume and neurological deficits |
| Route: Intravenous | Promoted neuronal growth, axonal regeneration and synaptic remodelling | |
| Time of administration: Not available | ||
| miR-200c antagomir | Model: MCAO mice | Increased neuronal survival rates through directly binding to Reelin |
| (Stary et al.) | Delivery strategy: NA | Reduced infarct volume and neurological deficits |
| Route: intraventricular | ||
| Time of administration: 24 h before MCAO | ||
| miR-214 agomir | Model: MCAO mice | Inhibited neuronal cell death by directly binding to Bax protein |
| (Ping et al.) | Delivery strategy: NA | Improved neurological outcomes and reduced infarct volume |
| Route: intraventricular | ||
| Time of administration: 48 h before MCAO | ||
| miR-216a agomir | Model: MCAO mice | Downregulated pro-inflammatory mediators, e.g. iNOS, MMP-9, TNF and IL-1β by directly targeting JAK2/STAT signalling pathway |
| (Tian et al.) | Delivery strategy: NA | Improved functional outcomes and reduced infarct volume |
| Route: intraventricular | ||
| Time of administration: 10 min after MCAO | ||
| miR-365 antagomir | Model: MCAO rats | miR-365 targets Pax6, a transcription factor account for conversion of astrocytes to neurons |
| (Mo et al. 2018) | Delivery strategy: NA | Promoted neurogenesis by inducing new mature neuron generation derived from astrocytes in the ischemic striatum |
| Route: intraventricular | Reduced neurological deficits and infarct outcome | |
| Time of administration: 30 min after MCAO | ||
| miR-384-5p agomir | Model: MCAO mouse | Promoted proliferation and angiogenesis of EPCs by regulating Notch signalling pathway |
| (Fan et al. 2020) | Delivery strategy: NA | Decreased infarct size and neuronal cell death |
| Route: Intraventricular | ||
| Time of administration: 2 days before MCAO | ||
| miR-1906 agomir | Model: MCAO mice | Reduced post-stroke inflammatory response by directly targeting TLR-4 |
| (Xu et al. 2017) | Delivery strategy: NA | Decreased neurological deficits and infarct volume |
| Route: intraventricular | ||
| Time of administration: not provided | ||
| miR-3473b antagomir | Model: MCAO mouse | Prevented neuroinflammation by downregulating mRNA and protein expression of pro-inflammatory mediators like iNOS, COX-2, TNF and IL-6 |
| (Wang et al. 2019) | Delivery strategy: NA | Reduced infarct volume and improved neurobehavioural recovery |
| Route: intraventricular | ||
| Time of administration: 3 days prior to MCAO |
AMPK 5′ adenosine monophosphate-activated protein kinase, Cdc42 cell division control protein 42, COX-2 cyclooxygenase-2, eNOS endothelial nitric oxide synthase, EPCs endothelial progenitor cells, IL-1β interleukin-1β, IL-6 interleuikin-6, iNOS inducible nitric oxide synthase, JAK janus kinase, JNK c-Jun N-terminal kinase, KLF-5 kruppel-like factor, MCAO middle cerebral artery occlusion, miRNA microRNA, MMP-9 matrix metallopeptidase-9, mRNA messenger ribonucleic acid, NA not applicable, NF-κB nuclear factor-κB, NO nitric oxide, Pax6 paired box protein-6, PI3K phosphoinositide 3-kinases, rAAV2/EGFP recombinant adeno-associated virus vector/E-green fluorescent protein, ROS reactive oxygen species, Sema3A semaphorin 3A, STAT signal transducer and activator of transcription, TLR-4 toll-like receptor-4, TNF tumour necrosis factor, VCAM-1 vascular cell adhesion protein-1, VEGF vascular endothelial growth factor