Table 2.

Survey of completed studies investigating different causes and treatments for carotid artery stenosis and middle cerebral artery occlusion

Claim	Method	Result	Ref
Carotid artery stenosis (CAS)
Statins lower LDL and stroke risk	Clinical trial	Atorvastatin lowered LDL compared to placebo (1.9 mmol/L down from 3.3 mmol/L, P < 0.001)	[188]
		Atorvastatin reduced stroke risk compared to placebo (11.2% incidence down from 13.1%, P = 0.03)
	Clinical trial	Rosuvastatin lowered LDL by 50% (P < 0.001)	[189]
		Rosuvastatin reduced cardiovascular events by 43% (P < 0.00001)
Surgical procedures lower stroke risk	Clinical trial	In asymptomatics, CEA lowered cardiovascular event risk compared to deferred CEA (4.1% down from 10.0%)	[192]
		Greatest net benefit from CEA was identified in those also on lipid-lowering therapy
	Clinical trial	In asymptomatics, CEA + aspirin/medical management lowered cardiovascular event risk compared to aspirin/medical management alone (5.1% down from 11.0%)	[193]
Antibody action lowers LDL	Clinical trial	Evolocumab lowers LDL by 59% (0.78 mmol/L down from 2.4 mmol/L, P < 0.001)	[190]
	Clinical trial	Inclisiran lowers PCSK9 and LDL cholesterol levels (reductions of 35.5–52.6% after two doses, P < 0.001) for patients at high cardiovascular risk	[208]
Genomics predicts carotid artery lumen diameter	GWAS	In the Arizona Strong Heart Family Study, genomic loci on chromosomes 7 and 12 were found to be significantly associated with left carotid artery diastolic and systolic lumen diameters	[194]
Genomics predicts moyamoya disease susceptibility	GWAS	Ten genomic loci were identified as significantly linked to moyamoya disease, including previously characterized loci on chromosome 17q25	[195]
	GWAS	In a Japanese cohort, the RNF213 gene on chromosome 17q25 was found to be highly associated with moyamoya disease	[196]
miRNA transcriptomics predicts stroke risk	miRNA association study	In asymptomatics, five miRNAs were identified as significantly overexpressed in patients with disease progression compared to those without	[197]
Biological modelling of CAS is in its infancy	Network	fMRI-based functional network	[198]
	Network	Doppler sonogram-based neural network	[199]
Middle cerebral artery occlusion (MCAO)
Brain metabolic activity is altered post-MCAO	NMR	In rats, MCAO resulted in increased lactose, alanine, glutamine and GABA and decreased aspartate, glutamate, succinate and creatine due to increased glycolysis and decreased TCA flux	[203]
	MS imaging	In mice, MCAO resulted in increased phosphocreatine, creatine and ceramide. Effects were most pronounced in the caudoputamen and cortex and least pronounced in the hippocampus	[204]
Brain RNA content is altered post-MCAO	RNA-seq	lncRNA-mRNA co-expression network based on rat data, showing lncRNA regulatory changes post MCAO	[202]
	Microarray	Circular RNAs, a lesser-studied class of ncRNA, are differentially expressed in mice post-MCAO	[201]
	RNA-seq	In mice, astrocytes respond to MCAO by upregulation of genes associated with complement and coagulation cascades, scar formation, inflammation, and apoptosis	[200]
		Jak/Stat signalling was upregulated; knocking out STAT3 resulted in increased neuron survival after MCAO
MCAO induces protein aggregation	MS	In mice, following MCAO, proteins associated with DNA/RNA processing and signal transduction increased in insolubility, indicating protein aggregation	[209]
Neuroprotective drugs mitigate MCAO effects	2DGE/MS	In mice, quercetin mitigated the drop in ICDH, adenosylhomocysteinase, pyruvate kinase, and UCH-L1, and the increase in HSP60 and CRMP-2 protein expression as a result of MCAO	[205]
	2DGE/MS	In rats, resveratrol mitigated the drop in Prx-5, ICDH, ApoA-1 and UCH-L1, and the increase in CRMP-2 as a result of MCAO	[210]

ApoA-1, apolipoprotein A1; CAS, carotid artery stenosis; CEA, carotid endarterectomy; CRMP-2, collapsing response mediator protein 2; fMRI, functional magnetic resonance imaging; GABA, gamma-aminobutyric acid; GWAS, genome-wide association study; HSP60, heat shock protein 60; ICDH, isocitrate dehydrogenase; LDL, low-density lipoprotein; lncRNA, long non-coding RNA; MCAO, middle cerebral artery occlusion; miRNA, microRNA; MS, mass spectrometry; ncRNA, non-coding RNA; NMR, nuclear magnetic resonance, PRX-5, peroxisome assembly factor 5; RNF213, Ring Finger Protein 213; STAT3, signal transducer and activator of transcription 3; TCA, tricarboxylic acid cycle; UCH-L1, ubiquitin carboxy-terminal hydrolase L1; 2DGE, 2D Gel Electrophoresis.