Article Contents
Clin Exp Pediatr > Volume 68(7); 2025 |
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Cell line | Model/inducer | Outcome | Mechanism | References |
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BV2 microglia cell line | OGD | Caspase-1 ↑, GSDMD ↑ | HMGB1/RAGE/Catepsin | [24] |
Primary microglia from 1- to 2-day-old CD1 mice | Free bilirubin for 24 hr | HMGB1↑, TNF-α↑, IL-1β↑, IL-6↑, IL-10↑, Arg1↑ | - | [35] |
Primary microglia from cerebral cortex of neonatal rats | Unconjugated bilirubin for 24 hr | NLRP3 ↑, ASC ↑, IL-1β ↑ | Akt–mTOR | [36] |
N9 microglia cell line | Bilirubin and LPS for 6 hr | NLRP3 ↑, Caspase-1 ↑, IL-1β ↑ | - | [37] |
Primary microglia postnatal day-1 rat | LPS for 24 hr | NLRP3 ↑, ASC↑, Caspase-1↑, TNF-α↑, IL-1β↑, IL-6↑ | miR-374a-5p – Smad6 | [20] |
Primary microglia culture from 1/3-day-old rats | LPS for 24 hr | NLRP3↑, ASC↑, Caspase-1↑, IL-1β↑, IL-6↑, TNF-α↑ | - | [39] |
Primary microglia from postnatal day-1 rat | LPS and serum amyloid A protein for 1–24 hr | NLRP3 ↑, IL-1β ↑ | P2X7R | [40] |
A microglial cell line derived from C57BL/6 mice (NR-9460) | NMEC RS218 | IL-1β↑, IL-1α↑ | TLR4/Myd88 | [41] |
Primary mouse cortical astrocytes from P0 mice | OGD | NLRP3↑, ASC↑, Caspase-1↑, TNF-α↑, IL-1β↑, IL-6↑, IL-10↑ | JAK2-STAT3 | [42] |
Rat hippocampal astrocytes from 1-day-old rats | OGD | NLRP3↑, ASC↑, Caspase-1↑, GSDMD↑, IL-1β↑, IL-18↑ | miRNA-148a-3p | [43] |
STAT/JMJD3 axis | ||||
Primary cortical astrocytes from 3-day-old rats | Unconjugated bilirubin for 6 and 12 hr | Caspase-1 ↑, NLRP3 ↑, IL-1β ↑, IL-18 ↑ | - | [44] |
PC12 rat pheochromocytoma cells | OGD | NLRP3↑, ASC↑, GSDMD↑, IL-1β↑, IL-18↑ | - | [46] |
PC12 rat pheochromocytoma cells | CoCl2 for 24 hr | NLRP3↑, ASC↑, Caspase-1↑, TNF-α↑ , IL-1β↑, IL-6↑, IL-18↑, NfκB↑ | - | [22] |
PC12 rat pheochromocytoma cells | OGD | NLRP3↑, ASC↑, Caspase-1↑ | - | [47] |
Primary neuron culture from D18 rat fetus brain | OGD | Caspase-1 ↑, NLRP3 ↑, IL-1β ↑ | - | [48] |
ASC, apoptosis-associated speck-like protein containing a Caspase recruitment domain; GSDMD, Gasdermin D; HMGB1, high mobility group box 1; IL, interleukin; LPS, lipopolysaccharide; NF-κB, nuclear factor κB; NLRP3, NOD-like receptor family pyrin domain containing 3; NMEC, neonatal meningitis-associated Escherichia coli; OGD, oxygen/glucose deprivation; TNF-α, tumor necrosis factor-alpha.
Model | Outcome | Pathway | References |
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Neonatal HIBD in mice | NLRP3 ↑ | [49] | |
Neonatal HIBD in NLRP3‒/‒ and ASC‒/‒ mice | NLRP3‒/‒ mice had more activated microglia than Wt mice, but ASC‒/‒ animals had less active microglia | - | [50] |
Neonatal HIBD in a rat model with, NLRP3 inhibitor | MCC950, NLRP3 inhibitor, significantly reduced pyroptosis in a rat model of neonatal HIBD | - | [21] |
Neonatal rat model of inflammation-sensitized HIBD | IL-1β, IL-6, iNOS, and TNF-α, Arg1, CCL11, IL-1, and TGF-β and NLRP3↑ in sorted CD11b/c microglia of brain samples | - | [51, 52] |
Neonatal HIBD in a rat model | Caspase-1, IL-1β, IL-18↑ | - | [51, 52] |
NLRP3 expression ↑ at 6 hr to 24 hr after HI, which declined 48 h after HI. | |||
Neonatal HIBD model with Gingko Biloba | IL-1β, IL-18↑ | - | [56] |
NLRP3↑ | |||
Caspase-1 and the nuclear translocation of NFκB P65↑ | |||
Neonatal HIBD in a rat model with IRE1α inhibitor | TXNIP/NLRP3 inflammasome activation | TXNIP/NLRP3 - miR-17-5p | [57] |
White matter damage (WMD) caused by endotoxin and ischemic hypoxia in neonatal rats | NLRP3, IL-1β and IL-18 ↑ | TLR4/NFκ-B pathway | [58] |
Neonatal HIBD in a rat model with N-acetylserotonin derivative | NLRP3↑ | PI3K/Akt/Nrf2 pathway | [59] |
Neonatal HIBD in a rat model with neferine | Caspase-1, ASC, GSDMD, TNFα, IL-β, IL-18, IL-6 ↑ | - | [22] |
HI-induced model of cerebral white matter damage (WMD) | NLRP3, Caspase-1, IL-1β, TNFα, IL10 ↑ | - | [48, 51-55] |
HI-induced model of cerebral white matter damage (WMD) with caffeine | NLRP3 inflammasome activation in neonatal rats | - | [54] |
Neonatal rat model of inflammation-sensitized HIBD | NLRP3, CXCL1 and CXCR2↑ | CXCL1/CXCR2 pathway | [43, 60] |
Neonatal HIBD in a rat model with Dexmedetomidine | IL-1β and IL-18 cytokine levels and NLRP3, ASC, Caspase-1, GSDMD ↑ | - | [43] |
Rat model of neonatal sepsis with rCC16 (recombinant club cell protein) | NLRP3, Caspase-1, TNFα, IL-1β and IL-6 levels, phosphorylated p38-MAPK and ERK ↑ | - | [63] |
HI in Wt and Nrf2‒/‒ mice | NFκB and NLRP3↑ | - | [61] |
Neonatal HIBD in a rat model with maternal treadmill exercise | NLRP3, Caspase-1 ↑ | - | [53] |
Neonatal hyperoxia in mice | NLRP3, IL-1β, Caspase-1 ↑ | - | [37] |
Neonatal bilirubin-induced neuronal damage (BIND) model in rats with rapamycin | NLRP3 and ASC protein ↑ | - | [36] |
Neonatal BIND model in Nlrp3‒/‒, Caspase-1‒/‒ and WT mice | NLRP3, Caspase-1 and IL-1β↑ | - | [37] |
Diminished in knockouts | |||
Neonatal meningitis-associated Escherichia coli (NMEC). NLRP3‒/‒ and Caspase-1‒/‒ mice | IL-1b and IL-1a ↑ | - | [41] |
Diminished in knockouts | |||
Neonatal encephalopathy (NE) patients | IL-1ra, IL-18, NLRP3 and IL-1 ↑ | - | [64] |
Mice model of preterm brain injury | NLRP3 and IL-1β ↑ | - | [62] |
ASC, apoptosis-associated speck-like protein containing a Caspase recruitment domain; CXCL1, chemokine (C-X-C motif) ligand 1; CXCR2, C-X-C chemokine receptor 2; ERK, extracellular signal-related kinase; GSDMD, Gasdermin D; HI, hypoxia-ischemia; HIBD, hypoxia-induced brain death; IL, interleukin; iNOS, inducible nitric oxide synthase; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; NLRP3, NOD-like receptor family pyrin domain containing 3; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha, TXNIP, thioredoxin-interacting protein; Wt, wild-type.
Study type | Reagents | Mechanism of action | References |
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In vitro | Glycyrrhizin | HMG1 inhibitor | [24] |
Rapamycin | mTOR inhibitor | [36] | |
NLRP3 siRNA | siRNA | [37] | |
miR-374a-5p mimic | Targeting Smad6 | [20] | |
Osteopontin | Secretory extracellular matrix glycoprotein | [39] | |
A740003 | P2X7R antagonist | [40] | |
MCC950 | NLRP3 inhibitor | [41] | |
ZJU37 | RIP1/RIP3 inhibitor | [68] | |
Dexmedetomidine | α2-adrenoceptor agonist | [43] | |
VX-765 | Caspase-1 inhibitor | [44] | |
HIBDAP | Pyroptosis suppressor | [47] | |
Diallyl disulfide | Pyroptosis suppressor | [46] | |
In vivo | Gingko Biloba | NLRP3 supressor | [56] |
miR-17-5p | IRE1α supressor | [57] | |
MCC950 | NLRP3 inhibitor | [21] | |
Melatonin | TLR4/NF-κB pathway inhibitor | [58] | |
N-acetylserotonin | PI3K/Akt/Nrf2 pathway activator | [59] | |
Neferine | NLRP3 inflammasome activation supressor | [22] | |
Caffeine | A2aR antagonist | [54] | |
Dexmedetomidine | α2-adrenoceptor agonist | [43, 60] | |
Hydrogen | Activator of Nrf2-mediated NLRP3 and NF-κB pathways | [61] | |
rCC16 | Pyroptosis suppressor | [63] | |
Clinic | Anakinra | IL-1 receptor antagonist | [67] |
HMG1, high mobility group 1; IL, interleukin; IRE1, inositol-requiring transmembrane kinase/endoribonuclease 1α; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor κB; NLRP3, NOD-like receptor family pyrin domain containing 3; PI3K, phosphoinositide 3-kinase; RIP1, receptor-interacting protein 1; RIP3, receptorinteracting protein 3; siRNA, small interfering RNA; TLR4, Toll-like receptor 4.