TABLE 3.
Cell death in preclinical models of preterm white matter injury following inflammation.
| Species | Time of the insult | Model | Cell death markers (time post insult) | + Cell types | ROIs | Neuroprotectant | References |
| Sheep | 91 d ga | LPS (150 ng/kg), i.v., over 3 d | c-CASP3 (7 d) | n.d. | SCWM | hUCB cells | Paton et al., 2018 |
| 93–96 d ga | LPS (100 ng), i.v. | TUNEL, c-CASP3 (3 d), Cysts (30%) | Olig2, CNPase | CBWM | – | Dean et al., 2009 | |
| 109 d ga | LPS (150 ng/kg), i.v., over 3 d | Pyknotic nuclei (114 d ga) | n.d. | PVWM | hAECs | Yawno et al., 2017b | |
| 5 h, 12 h, 24 h, 2 d, 4 d, 8 d, or 15 d before preterm delivery at 125 d ga | 1 × LPS (10 mg), intra-amniotic | c-CASP3 (2 d to 15 d) | n.d. | WM, Hipp, CX | – | Gussenhoven et al., 2018 | |
| Rat | E17, 6 h before preterm delivery | LPS (1 mg/kg), maternal i.p. | c-CASP3 (6 h) | n.d. | n.d. | Fingolimod | Yavuz et al., 2017 |
| E18 | LPS (1 mg/kg), maternal i.p. | TUNEL (E20) | PDGFαR | SZ | NAC | Paintlia et al., 2004 | |
| E18+E19 | LPS (0.5 mg/kg.), maternal i.p., LPS (0.3 mg/kg.), maternal i.p. | -TUNEL, c-CASP3 (P6) -TUNEL, c-CASP3 (P7) -Impaired autophagy (P1) | n.d. | -PVWM -ST, PVWM, GV -Whole brain | -APC, EPO, SPD – – | Kumral et al., 2007, 2017, Yesilirmak et al., 2007,Rousset et al., 2006 Carloni et al., 2016 | |
| P3 | LPS, i.c. -(10 μg) -(1 mg/kg) | -Fractin (4 d) -RIP1, RIP3 and MLKL RNAs (1 d) -Fractin (1 d) |
-SMI-312 | -ST, -ST, SCWM, CC -Whole hemisphere -CG, CC | – | Ginet et al., 2016, Lodygensky et al., 2014,Pierre et al., 2019 | |
| P3 | LPS (0.25 mg/kg), i.p. | -c-CASP3, TUNEL (2d) | n.d. | -CX, SCWM extracts | -MSC-EVs | Drommelschmidt et al., 2017 | |
| P5 | LPS (10 μg), i.c. | -TUNEL (1 d) -Cysts (30%, injection site) | n.d. | -SCWM (near injection) -CC | -Minocycline – | Fan et al., 2005a | |
| P5 | LPS (2 mg/kg), i.p. | TUNEL, c-CASP3 (1 d) | O4 | CG | Celecoxib | Fan et al., 2013 | |
| P5 | IL-1β (10 ng), i.c. | -TUNEL, c-CASP3 (1d) | Lectin, O4, O1, NF | -Sub-ventricular area, CC, outer layers of CTX | -NBQX | Cai et al., 2004 | |
| Rabbit | 24–30 d ga | LPS, uterine horn, + ceftriaxone (+24 h) | -TUNEL (2 d) -Cysts (∼25–23%) | n.d. | -PVWM, CA2 -PVWM | – | Debillon et al., 2003, Debillon et al., 2000 |
| Rhesus macaque | 130 d ga, 16 h before preterm delivery | LPS (1 mg), i.a. | c-CASP3 | n.d. | PVWM | – | Schmidt et al., 2016 |
APC = activated protein C; CA = cornu ammonis; CBWM = cerebellar WM; c-CASP3 = cleaved caspase-3; CNPase = 2′,3′-cyclic nucleotide 3′-phosphodiesterase; CTX = cortex; d = day; E = embryonic day; ga = gestational age; GV = germinative ventricular zone; hAECs = human amnion epithelial cells; h = hours; Hipp = hippocampus; i.a. = intra-amniotic; i.c. = intracerebral; i.p. = intraperitoneal; i.v. = intravenously; LPS = lipopolysaccharide; MSC-EVs = mesenchymal stem/stromal cells; NAC = N-acetyl cysteine; n.d. = not defined; NF = neurofilament; O4, O1 = oligodendrocyte markers O4, O1; Olig2 = oligodendrocyte transcription factor; P = postnatal day; PDGFαR = platelet-derived growth factor-α receptor; PVWM = periventricular WM; ROIs = regions of interest (i.e., where cell death is detected); SCWM = subcortical white matter; SMI-312 = anti-neurofilament Marker (pan axonal, cocktail); SPD = surfactant protein; ST = striatum; SZ = subventricular zone; TH = thalamus; hUCB = human umbilical cord blood; WM = white matter; nd = not defined.