Cell Type-Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal-Regulating Kinase 1

Table 1

Genetic/pharmacological inhibition of ASK1. bEnd.3 cell line (mouse endothelial cells), BV2 cell line (mouse microglia cells), RAW 264.7 cell line (mouse macrophage cells), HAEC cells (human aortic endothelial cells), and MEF cells (mouse embryonic fibroblasts). MPO: myeloperoxidase; ICV: intracerebrovascular injection; IV: intravenous injection; IH: intrahemispheric injection.

Genetic/pharmacological inhibition of ASK1	Dosage	Application	Injury or duration	Main outcome	Reference
ASK1 knockout (KO)		ASK1 KO mice	Optic nerve injury	Eye: apoptotic cell death↓, MCP-1↓, TNF-α↓, iNOS↓	[77]
		MEF cells	H2O2 or TNF treatment	Apoptotic cell death↓	[96]
		Platelets		Thromboxane A2↓, platelet granule secretion↓	[22]
		ASK1 KO mice	FeCl3-induced injury	Carotid artery thrombosis↓	[22]
Small interfering RNA (siRNA) for ASK1	5 μM/mice (ICV)	C57/BL6 mice	3 days before ischemic/reperfusion (I/R) injury	Brain: brain edema↓, VEGF↓, AQP-1↓	[24]
	5 μM/mice (ICV)	C57/BL6 mice	3 days before I/R injury	Brain: neuronal cell death↓, MMP-9↓	[50]
	5 μM/mice (ICV)	C57/BL6 mice	3 days before I/R injury	Brain: GFAP↓, glial scar formation↓	[19]
	5 μM/mice (ICV)	C57/BL6 mice	3 days before I/R injury	Brain: IL-6↓,TNF-α↓, IL-1β↓	[23]
	5 μM/mice (ICV)	C57/BL6 mice	3 days before I/R injury	Brain: infarct volume↓	[21]
Nanoparticles with anti-ASK1 short hairpin RNA (shRNA)	150 μg/rat (IV)	Spraque-Dawley rats	2 days before I/R injury	Brain: apoptotic cell death↓, infarct injury↓	[101]
NQDI-1, ASK1 inhibitor	600 nM	bEnd.3 cell line	3 hrs before oxygen/glucose deprivation (OGD)	VEGF↓	[24]
	600 nM	bEnd.3 cell line	1 hr before OGD/6 hrs during OGD	Released MMP-9↓	[50]
	600 nM	BV2 cell line	1 hr before OGD/4 hrs during OGD	IL-6↓, TNF-α↓, IL-1β↓, iNOS↓	[23]
	600 nM	RAW 264.7 cell line	1 hr before OGD/4 hrs during OGD	IL-6↓, TNF-α↓, IL-1β↓, iNOS↓	[23]
	250 nmol/pup (IH)	Spraque-Dawley rats	30 mins before hypoxia-ischemia (HI) injury	Brain: caspase-3↓, infarct volume↓, apoptotic cell death↓	[100]
AGI-1067, ASK1 inhibitor	10 μM	HAEC cells	1 hr before LPS/during LPS treatment	VCAM-1↓, E-selectin↓, IL-6↓, MCP-1↓	[73]
Thioredoxin	2 μg/g (IV)	C57/BL6 mice	10 mins before ventilation	Infiltration of neutrophils↓, MPO↓	[75]
MSC2032964A, ASK1 inhibitor	10 μM	Primary microglia cells	1 hr before LPS treatment	TNF-α↓, iNOS↓	[77]