Table 2.

Animal studies reporting NF-κB status in IA animals compared to control animals.

	Animals	NF-κB Activation	Inflammatory Markers and MMPs	IA Features	Ref.
1	Rats	Higher NF-κB P65 mRNA expression, increased protein levels of NF-κB p-p65	Higher mRNA levels of TLR4, Poly (ADP-ribose) polymerase-1 (PARP-1), TNF-α, inducible nitric oxide synthase (iNOS), MMP-2, and MMP-9, increased protein expression of TLR4 and PARP-1	Stratification in the cerebral artery wall, decreased SMCs, inward depressing exited in the vascular wall, infiltration, and accumulation of macrophages, neutrophils, and T cells	[23]
2	Rabbits	Increased NF-κB-p65 staining intensity	MMP-2 and MMP-9 in SMCs, increased staining intensity of MMP-2, MMP-9, and MCP-1, lower smooth muscle actin (SMA) and calponin	IEL loss, media thinning, and bulge formation within one week, larger zones of media thinning and bulging 6 months later	[24]
3	Rats	Higher mRNA and protein expression of NF-κB P65 and lower mRNA and protein expression of IκBα, increased NF-κB p65 phosphorylation	Higher mRNA protein expression of MMP-2, MMP-9, TNF-α, IL-1β, Il-6, and lower mRNA and protein expression of APC	Damaged endothelium, degenerated VSMCs, lower number of VSMCs and its layers, thinner artery wall, fractured elastic fiber, and inflammatory cell infiltration	[11]
4	Rats	Higher mRNA expression of NF-κB in IA walls	Higher mRNA expression of MMP-2, MMP-9, MCP-1, and VCAM-1 in IA walls	Increased macrophage infiltration in IA walls	[25]
5	Rats	Higher levels of phosphorylated NF-κB P65 and IκBα, lower levels of IκBα protein	Decreased tumor necrosis alpha-induced protein 3 (A20) protein expression	Disrupted IEL	[26]
6	Mice	mRNA expression of NF-κB increased in unruptured IAs and even more in ruptured IAs	Myocardin, smooth muscle alpha-actin (SM-α-actin), smooth muscle myosin heavy chain (SM-MHC), and SM-22α mRNA levels decreased, while MCP-1, MMP-3, MMP-9, TNF-α, IL-1β, iNOS, VCAM, and Krüppel-like factor 4 (KLF4) increased in unruptured IAs and even more in ruptured IAs	Layers of discontinuous endothelial cells and scattered VSMCs, disorganized elastic lamina, macrophage infiltration, and NADPH oxidase-1 (NOX1) immunoreactivity was significantly higher in unruptured IAs, and highest in ruptured IAs, colocalizing with both SMCs and macrophages	[14]
7	Rabbits	Increased the protein expression of phosphorylated inhibitory-κB kinase alpha (p-IKKα) and t-IKKα and positive expression rate of NF-κB P65	Decreased eNOS mRNA expression and increased iNOS mRNA expression. Staining intensity and mRNA expression of MMP-2 and MMP-9 increased. The expression of Th17-related factors RORYT, IL-17, IL-22, IL-23, and RORC were increased, and the expression of Treg-related factors IL-10, TGF-β, and Foxp3 was decreased, increased protein expression of t-PI3K, p-PI3K, t-AKT, p-AKT.	Increased length of IEL loss and media thinning, reduced SMCs, broken elastic fibers, staining intensity, and mRNA expression of α-SMA was decreased. The number of Th17 cells was increased and the number of Treg cells was decreased in IA walls.	[20]
8	Rabbits	The mRNA and protein expression of NF-κB peaked one week after IA induction.	The mRNA and protein expression of MCP-1 peaked one week after IA induction. MMP-9 protein expression increased gradually.	Fractured elastic fiber, lower number of SMCs, damaged endothelial cells	[27]
9	Rats	NF-κB p65 expression colocalized with MCP-1	MCP-1 expressed in intima, media, and adventitia, localized to IA walls, increase in MCP-1 protein expression with IA progression	Macrophage accumulation in IA walls increased with IA progression.	[28]
10	Rats	Increased mRNA expression of NF-κB	Increased mRNA expression of MMP-2, MMP-9, VCAM-1, MCP-1 and decreased mRNA expression of eNOS and (issue inhibitor matrix metalloproteinase 1 (TIMP-1)	Increased macrophage infiltration and increased SMC apoptosis, decreased mRNA expression of B-cell lymphoma 2 (Bcl-2), and increased mRNA expression of iNOS	[29]
11	Rats	Increased staining intensity for NF-κB P65, NF-κB was activated in both endothelial cells and macrophages	MCP-1 and VCAM-1 costained with NF-κB P65		[8]
12	Mice	Increased protein expression of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and NF-κB P65, increased phosphorylation of STAT3 and NF-κB P65	Increased relative mRNA expression and release of TNF-α, IL-1β, IL-6, MCP-1, and IFN-γ and reduced IL-10 Reduced mRNA expression of MHC, SMA, and SM22 and increased mRNA expression of MMP-2 and MMP-9		[30]
13	Rats	increased mRNA expression of NF-κB	Increased concentration of IL-1β, IL-2, IL-6, IL-8, IL-17, and TNF-α, and increased MMP-2 and MMP-9 levels in IA walls, increased IFN-γ and SM22, increased NAD(P)H quinone dehydrogenase 1 (NQO-1) levels Decreased cytoplasmic nuclear factor erythroid-2-related factor (Nrf)-2 and increased nuclear Nrf-2	Increased macrophage infiltration and increased reactive oxygen species (ROS)	[31]
14	Rats	Increased DNA binding activities of NF-κB	Increased DNA binding activities of protein C-ets-1 (Ets-1)	Disrupted IEL and media thinning	[32]
15	Mice	Increased mRNA and protein levels of NF-κB	Increased mRNA and protein expression of MMP-2 and MMP-9	Decreased thickness of the arterial wall Increased macrophage infiltration	[33]
16	Rats	Increased protein expression and phosphorylation of NF-κB P65	Expression of TLR10 mRNA gradually increased with cerebral aneurysm progression. mRNA, protein expression, and staining intensity of TLR-4 increased in IA walls after one month and decreased after three months. Expression of TLR4 coincided well with NF-κB P65 activation.		[34]