Table 1.

Potential therapeutic strategies of WMI after ICH based on NLRP3 inflammasome inhibition.

Potential Inhibitor of NLRP3		Mechanism of Action	References
Compounds targeting specific pathways	BBG	Inhibiting P2X7R/NLRP3 axis.	[26]
	H2S	Attenuating NLRP3 inflammasome-mediated neuroinflammation by inhibiting P2X7R.	[103]
	5-BDBD	Alleviating WMI after ICH by M2 microglial polarization and increasing BDNF.	[53]
	MitoQ	Ameliorating WMI after ICH by suppressing mitochondrial ROS. Inhibiting the NLRP3 inflammasome to promote microglia polarization to the M2 phenotype.	[59, 101]
	Lithium	GSK-3β-mediated microglia phagocytosis and M2 phenotypic differentiation. Attenuating WMI following ICH through BDNF signaling.	[111, 128]
	APNp	Suppressing NLRP3 inflammasome activation in astrocytes via the AMPK/GSK-3β pathway.	[82]
	Scriptaid	Alleviating WMI following ICH by inhibiting HDAC through modulating microglial polarization.	[55, 129]
	Curcumin	Attenuating WMI caused by stroke through inhibiting NF-κB/NLRP3 inflammasome axis.	[102]
Small-molecule inhibitor	MCC950	Blocking ASC oligomerization, Suppressing of canonical and non-canonical NLRP3 inflammasome.	[10, 115, 116]
	OLT1177	Promoting myelin preservation by inhibiting NLRP3 inflammasome.	[132-135]
	ZJU-37	Promoting myelination by suppressing NLRP3 inflammasome.	[136]
Novel materials and cell therapy	PHBV/PLA/Col membrane	Reducing glial scar formation and promoting axonal regeneration by suppressing NLRP3 inflammasome activation and M1 macrophage polarization.	[139]
	CeNP	Attenuate WMI after ICH, and the mechanisms may be related to the involvement of microglia and astrocytes in myelin regeneration.	[71]
	Schwann cells	Inhibiting NLRP3 and NLRP1 inflammasome activation and promoting remyelination.	[140]
	hOPCs	Inhibiting NLRP3 inflammasome combined with ZJU-37 treatment.	[136]
Knock-out of certain genes	Drp1	Abolishing NLRP3 inflammasome activation and correcting myelin loss.	[123]
	TRPM2	Protecting from cuprizone-induced demyelination, activation of microglia, and NLRP3 inflammasome activation.	[124]
	UCP2	Activating NLRP3 inflammasome in astrocytes.	[80, 81]
Other compounds	MLT	Inhibiting NLRP3-induced apoptosis in OLs.	[141]
	17β-Estradiol	Reducing demyelination and promoting myelin regeneration by promoting M2 microglia polarization and inhibiting NLRP3 inflammasome.	[142]
	Sinomenine	Alleviating demyelination and axonal injury by inhibiting NLRP3 inflammasome.	[143]
	VK-28	Attenuating WMI and promoting microglial polarization to the M2 phenotype.	[144]
	IL-33	Ameliorating WMI after ICH by promoting microglial polarization to the M2 phenotype.	[54]
	Deferoxamine	Attenuating WMI.	[147]
	Minocycline	Attenuating WMI.	[148]

Note: NLRP3, the NOD-like receptor family, pyrin domain containing 3; WMI, white matter injury; MitoQ, mitoquinone; BDNF, brain-derived neurotrophic factor; ASC, apoptosis-associated speck-like protein; interleukin-33; IL-18, interleukin-33; NF-κB, nuclear factor kappa B; P2X7R, purinergic 2X7 receptor; P2X4R, purinergic 2X4 receptor; ROS, reactive oxygen species; GSK-3β, glycogen synthase kinase 3β; HDAC, histone deacetylase; PHBV/PLA/Col, poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/collagen; CeNP, ceria nanoparticle; Drp1, dynamin-related protein 1; TRPM2, transient receptor potential melastatin 2; MLT, melatonin; APNp, adiponectin peptide; BBG, blue brilliant G; UCP2, uncoupling protein 2; hOPCs, human neural stem cells.