Oxidative Medicine and Cellular Longevity

Review Article

Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases

Table 1

Oxidative stress-mediated BBB disruption in neurological diseases.


Diseases	Model	Targets		Pathways	Mechanisms	Ref
Diseases	Model	Oxidative stress	BBB	Pathways	Mechanisms	Ref

IS	MCAO, rat	MDA, GSH, and NADPH	ZO-1 and occludin	REK	Oxidative stress and tight junctions	[146]
	MCAO, rat	NOX2, NOX4, ROS, MDA, GPx, and NO	Occludin, MMP-9, Nrf2, and Nqo1	MAPK	MMP, oxidative stress, and inflammatory response	[147]
	OGD/R, BMVECs	ROS	ZO-1 and claudin-5	PI3K/Akt/Nrf2	Oxidative stress	[148]
	MCAO, rat; OGD/R, primary cortical neurons	NO, MDA, and ROS	IL-6 and TNF-α	NF-κB	Neuroinflammation and oxidative stress	[149]
	MCAO, rat; OGD/R, BMVECs	ROS	ZO-1	mTOR	Cell autophagy and oxidative stress	[150]

Hemorrhagic stroke	Autologous blood injection, rat	ROS	ATP, Bcl-2, Bax, caspase-3, and caspase-9	DJ-1/Akt/IKK/NF-κB	Apoptosis, oxidative stress, and inflammatory response	[151]
	Collagenase injection, rat	ROS, GSH-px, and SOD	ZO-1 and occludin	MAPK	Oxidative stress	[152]
	LPS-activated, microglia	ROS, NOX2, and NOX4	CD86, Arg1, CD206, IL-1α, IL-1β, TNF-α, and FeSO4	Not mentioned	Oxidative stress, inflammatory response, and iron metabolism	[153]
	Autologous blood injection, rat; OxyHb, primary rat cortical neurons	ROS, NOX1, and NOX2	TNF-α, MMP-9, NQO1, Bcl-2, Bax, caspase-3, CD14, CD68, γ-H2AX, and XRCC1	HO-1	Oxidative stress, apoptosis, inflammation, mitochondria injury, and DNA damage	[154]

TBI	Free fall brain trauma, rat	ROS, SOD, and 4-HNE	MMP-9, ZO-1, and occludin	JNK	MMP inhibition and oxidative stress	[155]
	A cryogenic injury, mice; biaxial stretch SI, BMVECs	ROS	GFAP, IL-6, IL-β, and ICAM-1	Nrf2/HO-1 and NF-κB	Oxidative stress and inflammatory response	[156]
	Controlled cortical, mice	SOD, CAT, and GSH	TNF-α, NLRP3, caspase-1, IL-1β, and IL-6	AMPK and Nrf2	Oxidative stress, inflammation, and apoptosis	[157]
	Controlled cortical, mice	SOD, GPx, and MDA	NQO1 and Bax	Nrf2-ARE	Oxidative stress and apoptosis	[158]

AD	Neuronal damage, neurons	ROS, 4HNE, H₂O₂, SOD, MDA, and GPx4	MMP	Nrf2/HO-1	MMP inhibition and oxidative stress	[159]
	H₂O₂-induced N2a, SH-SY5Y cells	ROS	Fe²⁺ and Fe³⁺	Nrf2/HO-1	Iron metabolism and oxidative stress	[160]
	Injection of D-galactose and Aβ25-35-ibotenic acid, rats	SOD, MDA, and GSH-Px	5-HT, methionine, glutamine, and tryptophan	AMPK-SIRT	Oxidative stress and energy metabolism	[161]
	H₂O₂-induced, PC12 cells	ROS	Caspase-3, MMP	ASK1-JNK/MAPK	MMP inhibition, apoptosis, and oxidative stress	[162]
	Aβ-induced, rats and SH-SY5Y cells	ROS	TXNIP	Not mentioned	Oxidative stress	[163]

PD	People, blood	ROS	P-gp	Not mentioned	Oxidative stress	[164]
	H₂O₂-induced, rat and PC12 cells	SOD and catalase	Caspase-3 and Hsp-70	Nrf2/HO-1	Oxidative stress and apoptosis	[165]
	6-OHDA-treated, mice	DA, ROS, and SOD	IL-1β and TNF-α	PI3K/AKT and IKK/IκBα/NF-κB	Neuronal inflammation and oxidative stress	[166]
	6-OHDA-induced, mice and SH-SY5Y cells	ROS and GSH	Caspase-3, Bax, and Bcl-2	Nrf2/HO-1	Oxidative stress and apoptosis	[167]
	MPTP-induced, mice and PC12 cells	ROS	Mitochondrial membrane potential and caspase-3	ROS/JNK	Oxidative stress and apoptosis	[168]

ALS	hSOD1-linked, Drosophila and NSC-34 cells	GSH and GCLC	HSP70	Nrf2/STAT3	Oxidative stress	[169]
ALS	SOD1 mutation, B6SJL-Tg 1Gur/J mice	COX, LDH, thiol groups, and lipid dienes	Cav-1, respiratory capacity rate, and cholesterol	Not mentioned	Mitochondrial bioenergetics and oxidative stress	[170]

CSVD	Spontaneously hypertensive, rat	SOD, GSH, MDA, and CAT	IL-6, TNF-α, IL-1β, Bcl-2, caspase-3, and VEGF	STAT3/VEGF	Oxidative stress and inflammatory response	[171]
CSVD	Spontaneously hypertensive, rat	SOD, GSH, MDA, and CAT	TNF-α, IL-6, IL-1β, MCP-1, and COX-2	Not mentioned	Oxidative stress and inflammatory response	[172]

Abbreviations: OGD/R: oxygen-glucose deprivation/reperfusion; MCAO: middle cerebral artery occlusion; OxyHb: Oxygen hemoglobin; SI: stretch injury; SH-SY5Y: human neuroblastoma cells; 4HNE: 4-hydroxynonenal; DA: dopamine; GCLC: glutamate-cysteine ligase catalytic; Bcl-2: B cell lymphoma-2; Bax: Bcl-2-associated X protein; Arg1: arginase 1; XRCC1: X-ray repair crosscomplementing gene 1; GFAP: glial fibrillary acidic protein; NQO1: NAD(P)H:quinone oxidoreductase; 5-HT: 5-hydroxytryptamine; TXNIP: thioredoxin-interacting protein; VEGF: vascular endothelial growth factor; Hsp-70: heat shock protein 70; Cav-1: caveolin-1; COX-2: cyclooxygenase-2; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; HO-1: heme oxygenase-1; SIRT: sirtuin; ASK1: apoptosis signal-regulating kinase 1; PKC: protein kinase C.