Table 3.

Pharmacotherapy can promote post-stroke recovery by targeting microglia. ↑, upregulate; ↓, downregulate; Gal-3, galectin-3, MCAO/R, middle cerebral artery occlusion/reperfusion; tMCAO, transient MCAO; dMCAO, distal MCAO; pMCAO, permanent MCAO; PT, photothrombosis; OGD/R, oxygen-glucose deprivation/reperfusion; LPS, lipopolysaccharide; IL-1β, interleukin-1β; IL-18, interleukin-18; NLRP3, NOD-like receptor thermal protein domain associated protein 3; TNF-α, tumor necrosis factor-α; IL-10, interleukin-10; TGF-β, transforming growth factor-β; Ym1, chitinase-like protein 3, IL-6, interleukin-6; iNOS, inducible nitric oxide synthase; Arg-1, arginase-1; IFN-γ, interferon-γ; IL-17, interleukin-17; IL-4, interleukin-4; MCP-1, monocyte chemotactic protein-1; MMP9, matrix metalloproteinase 9; NO, nitric oxide; COX-2, cyclooxygenase-2; STAT1, signal transducer and activator of transcription 1; STAT6, signal transducer and activator of transcription 6; NF-κB, nuclear factor kappa-B; TLR4, toll-like receptor 4; STAT3, signal transducer and activator of transcription 3; JAK2, Janus kinase 2.

Drug	In Vivo		In Vitro		Effect on Microglia	Signal	Reference
	Animal Model	Treatment	Cell Culture	Treatment
Minocycline	Mouse (tMCAO)	Intraperitoneal injections after MCAO induction; 10, 25, and 50 mg/kg/day for 3 consecutive days	BV2 microglial cells oxygen–glucose deprivation/reoxygenation (OGD/R) cell model	Minocycline at doses of 0.01, 0.1, 1, 10, and 100 μM; preincubated 1 h before OGD/R injury	IL-1β↓, IL-18↓, NLRP3↓		[239]
	Rats (tMCAO)	Intravenous injection after reperfusion onset; a single dose (3 mg/kg)			IL-1β↓, TNF-α↓, IL-10↑, TGF-β↑, Ym1↑		[240]
	Mouse (MCAO/R)	Intraperitoneal injections after reperfusion; 10, 25, or 50 mg/kg/day for 2 weeks	Primary microglia from cerebral cortex of newborn mice	LPS (100 ng/mL) + IFN-γ (20 ng/mL) + minocycline (50 μM); incubation for 24 h	IL-1β↓, IL-6↓, iNOS↓, TNF-α↓, Arg-1↑, IL-10↑, TGF-β↑, Ym1↑	STAT1/STAT6 pathways ↓	[241]
Wnt-3a	Mouse (tMCAO)	Intranasally delivered at the time of reperfusion and next 2 days; 2 μg/kg/day			iNOS↓, TNF-α↓, Arg-1↑, CD206 ↑		[242]
Gal-3	Mouse (MCAO)	Intracortical injection at 24 h following MCAO; 100 ng/mouse (20–25 g)	Primary cell cultures from the brains of the adult, 8–9-week-old C57BL/6 wild-type mice	Incubation with Gal-3 (5 μM) for 24 h	TNF-α↓, IL-1β↓, IFN-γ↓, IL-17↓, iNOS↓, Ym1↑, IL-4 ↑, IL-6 ↑		[243]
Atorvastatin	Mouse (pMCAO)	Oral gavage after MCAO induction; 20 mg/kg/day			IL-6↓, TNF-α↓, MCP-1↓, IL-10 ↑		[244]
Exendin-4	Mouse (MCAO)	Intraperitoneal injection; 50 mg/kg at 1.5 h after MCAO induction; 0.2 mg/kg daily for 3 days until sacrifice	Primary microglia-enriched cultures were prepared from whole brains of 2- to 3- day-old mice	LPS (10 ng/mL) + Ex-4 (40 ng/mL); incubation for 24 h	CD206↑, Arg-1↑, Ym1/2↑		[245]
Bendavia	Mouse (tMCAO)	Intraperitoneal injection immediately after reperfusion and 4 h later; 5 mg/kg			MMP9↓, TNF-α ↓		[246]
Vx-765	Mouse (MCAO)	intraperitoneal injection starting immediately after MCAO induction; 50 mg/kg for 3 consecutive days			IL-1β↓, TNF-α↓, iNOS↓, TGF-β↑, Ym1↑	NF-κB signaling↓	[247]
Baicalein	Mouse (MCAO)	Intragastrical administration after reperfusion; 100 mg/kg/day for 3 days	BV2 microglial cells	LPS (100 ng/mL) + IFN-γ (20 ng/mL) + baicalein (45 μM); incubation for 24 h OGD stimulated BV2 cells + baicalein (45 μM); incubation for 24 h	Ym1/2↑, Arg-1↑, CD206↑, TNF-α↓, IL-1β↓, IL-6↓, NO↓	TLR4/NF-κB ↓, phosphorylated STAT1 ↓	[248]
Cottonseed oil	Rats (MCAO/R)	Subcutaneous injection before MCAO; 1.3 mL/kg/day for 3 weeks			IL-1β↓, IL-6↓, TNF-α↓	TLR4/NF-κB ↓	[249]
GJ-4	Rats (MCAO/R)	Oral administration after MCAO induction; 10, 25, 50 mg/kg/day for 12 days			iNOS↓, COX-2↓, MMP9↓	JAK2/STAT1 ↓	[251]
Melatonin	Mouse (dMCAO)	20 mg/kg at 0 and 24 h after reperfusion	Co-culture of BV2 cells (growing on culture inserts) and OGD neuron	Melatonin (100, 200, or 400 mM); incubation for 12 h	pro-inflammatory markers ↓, anti-inflammatory markers ↑	p-STAT3/STAT3↑	[252]
Ki20227	Mouse (PT)	Oral gavage before modeling; 0.002 mg/kg/day for 7 consecutive days			TNF-α↓, iNOS ↓, IL-10↑, Arg-1 ↑, NLRP3↓, Active caspase 1 ↓	NF-κB signaling↓	[253]
Curcumin	Mouse (tMCAO)	Intraperitoneal injection; 150 mg/kg at 0 h and 24 h after reperfusion	BV2 microglial cells	LPS (100 ng/mL) + IFN-γ (20 ng/mL) + curcumin (12.5 and 25 µmol/L); incubation for 48 h	TNF-α↓, IL-12p70↓, IL-6 ↓		[255]
	Mouse (MCAO/R)	Intraperitoneal injection; 150 mg/kg/day for 7 days after ischemic stroke	Primary microglia were isolated from the whole brains of neonatal C57BL/6J mice	LPS (100 ng/mL) + curcumin (12.5 μM); incubation for 24 h		NLRP3/NF-κB pathway ↓	[256]