TABLE 8.
Cell death in preclinical models of iatrogenic preterm brain injury: hyperoxia.
| Species | Time of the insult | Model | Cell death markers (time post insult) | + Cell types | ROIs | Neuroprotectant | References |
| Rat | E21 | 80% O2 (8 d) | -TUNEL (P3) | -n.d. | -WM | -iNO | Pham et al., 2014 |
| E21 | 60% O2 (8 d) | -TUNEL (P3) | -n.d. | -WM | - | Vottier et al., 2011 | |
| P0 | 80% O2 (5 d) | -TUNEL, cell count (5 d) | -Neurons -Neurons |
-CA1, CA3 -CA1, DG, prefrontal/ parietal/ retrosplenial CTX, subiculum |
-Uridine -EPO -Topiramate |
Goren et al., 2017 Yis et al., 2008a Yis et al., 2008b Kurul et al., 2009 |
|
| P2 | 95% O2 (5 d) | -ELISA DNA fragm. | -n.d. | -CB, basal FB, frontal CTX, Hipp | -BSO | Taglialatela et al., 1998 | |
| 80% O2 -(1 d) |
-TUNEL, AIF (5 d) -c-CASP3 (1 d) -TUNEL -c-CASP3 -CASP2, 3, 8; silver staining -TUNEL (P7) |
-CC1 -n.d. -n.d. -MBP -n.d. -Olig2 |
-CC, CG, eC -CTX, WM -frontal/ retrosplenial CTX, HTH, TH -CC -CTX, STcn, NAcc, CC and adjacent WM, TH, Hipp, HTH - CC, deep cortical WM, CTX, TH |
-Minocycline -Dextromethorphan -Dexmedetomidine -17β-estradiol -EPO -EPO |
Schmitz et al., 2014 Posod et al., 2014 Sifringer et al., 2015 Gerstner et al., 2006 Gerstner et al., 2007 Kaindl et al., 2008 Hoeber et al., 2016 |
||
| P6 | -(1 d or 2 d) | -TUNEL, neuronal density -PARP-1, AIF, c-CASP3 |
-Nestin, DCX, NeuN -n.d. |
-Frontal/ retrosplenial/parietal CTX, TH, HTH -Whole brain |
-Caffeine -Caffeine |
Endesfelder et al., 2014 Endesfelder et al., 2017b |
|
| -(12 h or 1 d) | -CASP2, Cyc, APAF-1, AIF, BCL2, BID, c-CASP3, Fluoro-Jade B -BECN1, ATG3, ATG5, ATG12, LC3 |
-Neurons and n.d. -n.d. |
-TH -Whole brain |
-Caspase inhibitor (TRP601) -EPO |
Sifringer et al., 2012 Bendix et al., 2012 |
||
| -(2 h, 6 h, 12 h, 1 d, 2 d, and 3 d) | -c-CASP8, c-CASP3, Fas, FasL, FADD -Fluoro-Jade B, silver staining, CASP1 |
-n.d. -n.d. |
-CG, parietal CTX, CC, ST, TH | -CASP8 inhibitor (TRP801) -Recombinant IL-18BP |
Dzietko et al., 2008 Felderhoff-Mueser et al., 2005 |
||
| Mouse | P6 | 80% O2 -(2 h, 6 h, 12 h, 1 d, 2 d) -(1 d) |
-Fluoro-Jade B, silver staining -CASP2, CASP3, CASP8, silver staining |
-n.d. -n.d. |
-CG, parietal CTX, CC, ST, TH -CTX, STcn, NAcc, CC and adjacent WM, TH, Hipp, HTH |
-KO IRAK-4 -EPO |
Felderhoff-Mueser et al., 2005 Kaindl et al., 2008 |
| P6 | FasL + 80% O2 (1 d) | -c-CASP8, c-CASP3 | -n.d. | -Cingulate/parietal CTX, CC, ST, TH | -CASP8 inhibitor (TRP801) | Dzietko et al., 2008 | |
AIF = apoptosis-inducing factor; BSO = buthionine sulfoxide; CC = corpus callosum; c-CASP = cleaved caspase; CG = cingulum; CTX = cortex; Cyc = cytochrome c; d = day; DG = dentate gyrus; E = embryonic day; eC = external capsule; EPO = erythropoietin; FB = forebrain; h = hours; Hipp = hippocampus; HTH = hypothalamus; iNO = inhaled nitric oxide; KO IRAK-4 = mice deficient in IL-1 receptor–associated kinase 4 (IRAK-4); NAcc = nucleus accumbens; n.d. = not defined; P = postnatal day; recombinant IL-18BP = Recombinant interleukin–18 binding protein; ROIs = regions of interest (i.e., where cell death is detected); SCWM = subcortical white matter; ST = striatum; STcn = striatal caudate nucleus; TH = thalamus; WM = white matter.