Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke-Induced Oxidative Stress

Table 1

The structure of NADPH oxidase and the expression and role of NOX in the brain of the cerebral ischemia-reperfusion model.

NOX subtype	Neurovascular unit	NOX subunit	Experimental model	Ischemia time	Reperfusion time	Oxidation product	Effect	References
NOX2	Astrocytes, neurons, endothelial cell, vascular smooth muscle, microglial	gp91phox; p22phox; p67phox; p47phox; Rac	NOX2 KO mice	1.25 h	24 h/72 h	O2^−	+	Chen, H (2011) [34]
			NOX2 KO mice	0.5 h	23.5 h	O2^−	+	De Silva, T.M (2011) [47]
			Mosaicism NOX2 KO mice	2 h	24 h	O2^−	+	Tang, X.N (2011) [33]
			NOX2 KO mice	24 h	/	O2^−	/	Kleinschnitz, C (2010) [50]
NOX1	Astrocytes, neurons, microglial, endothelial cell	NOXO1; NOXA1; p22phox; Rac	NOX1 KO mice	1 h		O2^−	+	Kahles, T (2007) [24]
			NOX1 knockdown mice	14 d/28 d	/	O2^−	+	Choi, D (2015) [23]
			NOX1 KO mice	0.5 h	23.5 h	O2^−	-	Jackman, K.A (2009) [53]
			NOX1 KO mice	More than 2 h	22 h	O2^−	/	Kahles, T (2007) [24]
NOX4	Vascular smooth muscle, pericytes, astrocytes, neurons	p22phox	In vitro model of BBB	6 h	24 h	H2O2	+	Casas, A.I (2019) [20]
			NOX4 KO mice	1 h/1.5 h	24 h	H2O2	+	Kleinschnitz, C (2010) [50]
			NOX4 KO rat	7 d	/	H2O2	+	Kleinschnitz, C (2010) [50]
			Permanent brain ischemia model in mice	30 d	/	H2O2	-	Vallet, P (2005) [55]
NOX5	Endothelial cell	/	NOX5-KI mice	1 h	24 h	O2^−	-	Casas, A.I (2019) [20]
			HBMECs expressing NOX5	6 h	24 h	O2^−	-	Casas, A.I (2019) [20]

Abbreviations: ROS: reactive oxygen species; NOX: nicotinamide adenine dinucleotide phosphate oxidase; O₂⁻: superoxide anion radical; H₂O₂: hydrogen peroxide; KO: knockout; BBB: blood-brain barrier; HBMECs: human brain microvascular endothelial cells. +, brain protection/neuroprotection; -, brain damage/neurological dysfunction.