TABLE 1.
Cell death after WMI in human preterm brain from autopsy.
| Type of WMI | Country (years of sample collection) | GA | PNA | Pathological features | Cell death markers | + Cell types | ROIs | References |
| Diffuse PWMI | US | Not indicated PCA: 28 to 42 w | Not indicated | ↓ preOL (O4+), ↑ oxidative stress in O4+, no cortical neuronal loss | H&E, TUNEL c-CASP3, fractin IHC | O4 | DWM | Back et al., 2005 |
| Diffuse WMI | CA (1983–2000) | 25 to 39 w | < 1 to 22 w | ↓ immature OL, ↑ preOL (O4+ O1-); ↑ GFAP, CD44 and HA; ↑ Iba-1 necrotic foci (microcysts) 59% ↑ focal axonopathy | H&E c-CASP3 IHC axonopathy (β-APP, fractin) | n.d. | WM | Buser et al., 2012 |
| Diffuse WMI | US (2003-2010) | 22 to 42 w | < 1 to 9 w | ↑ GFAP, CD44 and HA; ↑ Iba-1 necrotic foci (microcysts) 36% ↑ Olig2, ↑ focal axonopathy | H&E, c-CASP3 IHC, axonopathy (β-APP, fractin, SMI-312 IHC) | n.d. | WM | Buser et al., 2012 |
| PVL Diffuse WMI | FR | -26 to 38 w -26 w | -0 d to 2.2 w -7 w | -cysts, ↑ Vimentin -↑ Vimentin | TUNEL | GFAP, Vimentin | CTX, PWM, SCWM | Gelot et al., 2009 |
| PVL | US (1997–1999) | 32.8 ± 3.1 w | 3.7 ± 4.1 w | ↑ WM and GM gliosis, focal necrosis; ↑ neuronal loss | H&E, GFAP IHC | n.d. | TH, Hipp, GP, cerebellar nuclei | Pierson et al., 2007 |
| PVL | United Kingdom | 24 to 28.9 w | 1 d to 5.1 w | ↑ GFAP, ↑ Iba-1, ↓ neurons, ↑ LC3-II | LC3-II IHC | n.d. | TH | Vontell et al., 2015 |
| PVL | US | 27 to 40 w | 0 to 64 w | ↑ gliosis (GFAP), ↑ CD68, ↑ protein nitration (O4+, O1+), ↑ oxidative stress (O4+, O1+ and GFAP+) | Hematoxylin, TUNEL, Oxydative stress | O4, O1 | WM | Haynes et al., 2003 |
| PVL | US | 25 to 40 w | 0 to 8 w | ↑12/15-LOX (O4+, O1+ and APC+) in diffuse PVL component ↑12/15-LOX (CD68+) in cyst | H&E, TUNEL, Oxydative stress | n.d. and 12/15-LOX+ | WM | Haynes and van Leyen, 2013 |
| PVL | US | 34.5 ± 1.1 w | 7.0 ± 3.5 w | Diffuse astrogliosis no overall differences in olig2, MBP, c-CASP3 and KI67 ↑ c-CASP3 in necrotic foci | H&E c-CASP3 IHC | n.d. | PWM | Billiards et al., 2008 |
| PVL | US(1993–2007) | 32.5 ± 4.8 w | 4.1 ± 6.6 w | ↑ gliosis (GFAP), ↑ CD68, ↓ neuronal density, ↑ axonal damage | H&E, fractin IHC | n.d. | TH | Ligam et al., 2009 |
| PVL | US | 36 ± 3 w | 7.5 ± 17 w | ↑ gliosis (GFAP), ↑ axonopathy, ↑ GM damage (TH31%, CTX15%) | H&E, β-APP IHC, fractin IHC | n.d. | WM, TH, CTX | Haynes et al., 2008 |
| PVL | US(1993–2007) | 33.9 ± 4.3 w | 5.9 ± 14.0 w | ↓ layer V cortical neurons (MAP2+) No difference in cortical thickness ↑ cortical gliosis (GFAP) | H&E, fractin IHC | MAP2 | CTX | Andiman et al., 2010 |
| PVL | US | 32.8 ± 4.1 w | 1.9 ± 2.3 w | ↓ granular neurons (MAP2+) | H&E | MAP2 | CWM, PWM, SP | Kinney et al., 2012 |
APC = adenomatous polyposis coli (mature OL); CA = Canada; CaR = calretinin; c-CASP = cleaved caspase; CTX = cerebral cortex; CWM = central white matter; d = day; DWM = deep white matter; FR = France; GA = gestational age at birth; GABA = g-aminobutyric acid; GAD = glutamic acid decarboxylase; GE = ganglionic eminence; GFAP = Glial fibrillary acidic protein; GM = gray matter; H&E = hematoxylin–eosin staining; Hipp = hippocampus; IHC = immunohistochemistry; LAMP1 = lysosomal-associated membrane protein 1; LC3 = microtubule-associated proteins 1A/1B light chain 3B; LOX = lipoxygenase; MAP2 = microtubule-associated protein 2; MBP = Myelin Basic Protein; n.d. = not defined; O1 = mature OL; O4 = immature preOL; OL = oligodendrocyte; PNA = postnatal age; PTL = perinatal telencephalic leukoencephalopathy; PVL = periventricular leukomalacia; PWM = periventricular white matter; PWMI = periventricular white matter injury; ROIs = regions of interest (i.e., where cell death is detected); SCWM = subcortical white matter; SP = subplate; TH = thalamus; United Kingdom = United Kingdom; US = United States; w = weeks; WM = white matter; WMI = white matter injury; + = positive.