Table 1.

Differential expression of circular RNA in IS.

Disease type	Model	Detection method	Change of expression profile	Specific core CircRNAs	Possible major biological processes and functions	Possible major signaling pathways/pathophysiological processes (target genes)	Refs.
Ischemic stroke	Mouse tMCAO model	Microarray analysis and qRT-PCR	1320 CircRNA differentially expressed (among them, 283 cases changed at least one reperfusion time point (> two times), 16 cases changed at all three reperfusion time points)	Three up (Circ_008018, Circ_015350, Circ_ 016128); three down (Circ_011137, Circ_001729, Circ_006696)	Biological regulation, metabolic processes, cellular communication, and binding to proteins, ions, and nucleic acids	Mitogen-activated protein kinase signal, cell cycle, actin cytoskeleton regulation, and local adhesion	Mehta SL et al. [17]
	Mouse tMCAO model	Microarray analysis and qRT-PCR	1027 CircRNA were differentially expressed, of which 914 were upregulated, and 113 were significantly downregulated	mmu_CircRNA_40001 mmu_CircRNA_013120 mmu_CircRNA_4080	Multiple biological processes, cellular signaling pathways, and protein activity	Ten paths, the first two were Rap1 signal pass and Hippo path	Liu C et al. [18]
	Peripheral blood of 80 AIS patients with different etiologies	Microarray analysis and qRT-PCR	1) Atherosclerotic and thrombotic stroke: 219 differential expressions; 2) Atherosclerosis and undetermined stroke: 87 upregulated and 139 downregulated; 3) Patients with thrombotic stroke and unconfirmed stroke: eight were upregulated, and nine were downregulated	HSA_CircRNA_102488	Differentially expressed CircRNAs interact primarily with a group of stroke-related miRNAs, including fatty acid biosynthesis, lysine degradation, arrhythmogenic right ventricular cardiomyopathy, or hypertrophic cardiomyopathy (HCM)	The RBP sites of hsa_CircRNA_102488 were clustered around AGO2 and FUS proteins	Aiora et al.[3]
	Mouse tMCAO model and peripheral blood of patients with AIS	Microarray analysis and qRT-PCR	There were 128,198,789 CircRNA changes at 5 min, 3 h, and 24 h after IS, respectively	CircBBS2, CircPHKA2	The biological processes related to stroke include immune process, metabolic process, and biological adhesion	Hippo signal Pathway, extracellular Matrix-receptor interaction, and Fatty Acid Metabolism	Lu D et al. [19]
	Permanent distal MCAO model in mice (non-ischemic ipsilateral thalamus)	Microarray analysis and qRT-PCR	2659 CircRNAs were differentially expressed (among them, 73 CircRNAs were significantly changed at seven and 14 days after stroke)	mmu_Circ:chr2:74568941-74573626, mmu_Circ: chr8:8639206-8639489, mmu_Circ:chr18:14633543-14636618	Closely related to inflammation and self-repair, CircRNA plays an important role in secondary thalamic nerve degeneration and remodeling after focal cortical infarction	Metabolic pathway, cancer pathway, PI3K-Akt signal pathway, endocytosis, mitogen-activated protein kinase signal pathway, Ras signal pathway, proteoglycan in cancer, Rap1 signal pathway, local adhesion, axon guidance, and other pathways	Li f et al. [25]
	PBMCs in AIS patients	HTS and qRT-PCR	521 Circ RNA differentially expressed (including 373 upregulated and 148 downregulated)	Four up (hsa_cic:chr1:95609447-95616975, hsa_cic:chr15:55640530-55640923); four down (hsa_cic:chr9:80869752-80879232)	Neuroinflammation and neuroimmunity	The pathways involved include metabolic pathways, mitogen-activated protein kinase signaling pathways, some inflammatory pathways, immune pathways, differentiation, and apoptosis-related signaling pathways	Dong Z et al. [20]
	OGD/R treatment of mouse hippocampal HT22 cells	Microarray analysis and QRT-PCR	Three upregulated and 12 downregulated	mmu-CircRNA-015947	-	Apoptosis, metabolism, and immune-related pathways	Lin SP et al. [24]
	Rat MCAO model (six left hemispheric brain tissues)	HTS and qRT-PCR	40 upregulated and 47 downregulated (four days after MCAO)	Three up (CircRNA.17737,CircRNA.8828,CircRNA.14479); three down (CircRNA.1059,CircRNA.9967, CircRNA.6952)	Nervous system development and endocytosis	Cytoplasmic vesicles, vesicles, synapses, cytoskeletons, cytoplasmic vesicles	Duan X et al. [21]
	Three AIS patients and three normal healthy controls	Microarray analysis and qRT-PCR	2270 CircRNAs were differentially expressed, of which 659 CircRNAs were upregulated, and 1611 were downregulated	hsa_Circ_0005548 significantly upregulated, hsa_Circ_0000607 and hsa_Circ_0002465 decreased significantly, hsa_Circ_0000607/mir-337-3p/BCL2 axis	-	Endocytosis, energy metabolism, apoptosis, FOXO signaling pathway, platelet activation, neurotrophic factor signaling pathway, and VEGF signaling pathway	LiS et al. [22]
	Five LAA stroke patients and four controls	Microarray analysis and qRT-PCR	182 CircRNAs upregulated and 176 downregulated	hsa_CircRNA_0001599	-	Chromatin modification, autophagy, platelet activation, and neural precursor cell proliferation	Li S et al. [23]