Table 3.

Preclinical attempts to target monocyte and microglia for treating AIS.

Target cell	Mechanism	Drug	Molecular targets	Outcomes	Reference
monocytes	Polarization regulation	5-BDBD	P2X4R	Reduced BBB leakage, infarct size neurological deficit	(242)
		N15	PPARα/γ		(243)
		1, 25-D 3	PPARγ		(244)
		rosiglitazone		Reduced BBB leakage and hemorrhagic transformation	(245)
		rhFGF21		Reduced infarct size and neurological deficit	(246)
		pamoic acid	GPR35		(247)
		DHA	?		(248, 249)
		AUDA	sEH		(250)
		miR-669c	MyD88		(251)
Microglia	Regulation of Activation and Polarization	ligustilide	TLR4		(252)
		miR-1906			(253)
		TAK-242			(254)
		eritoran		Reduced BBB disruption and infarct volume; improve functional outcome	(255)
		MTS510			(256)
		Ticagrelor	P2Y12R		(257)
		adjudin	NF-kB		(258)
		Statin	HMG-CoA reductase		(259–261)
		Minocycline	NLRP3		(262–265)
		Metformin	AMPK		(266–268)
	Cytokine inhibition	IL-1Ra	IL-1		(231)
		Canakinumab	IL-1β		(269)
		Infliximab	TNF-α		(143)

P2X4R, purinergic P2Y4 receptor; BBB, blood brain barrier; N15, Propane-2-sulfonic acid octadec-9-enyl-amide; PPARα/γ, peroxisome proliferator-activated receptor alpha/gamma; 1, 25-D 3, 1, 25-dihydroxyvitamin D3; rhFGF21, recombinant human fibroblast growth factor 21; NF-κB, nuclear factor kappa B; GPR35, G protein Coupled Receptor 35; Akt/p38 protein kinase B/p38 MAPK, mitogen-activated protein kinases; DHA, docosahexaenoic acid; AUDA, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid; sEH, soluble epoxide hydrolase; MyD88, myeloid differentiation primary response gene 88; TLR4, Toll-like Receptor 4; P2Y12R, purinergic P2Y12 receptor;NLRP3, NOD-like receptor family pyrin domain containing 3; AMPK, AMP-activated protein kinase; IL-1Ra, interleukin-1 receptor antagonist; IL-1, interleukin-1; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α.