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Published on: October 28, 2022
Apoptosis and white matter injury in preterm infants
Sangkae Chamnanvanakij1, Linda R Margraf, Dennis Burns
1Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9063, USA.
Insights
Apoptosis, programmed cell death, significantly contributes to white matter injury in premature infants with intraventricular hemorrhage (IVH) and periventricular echogenicity (PVE). Inhibiting apoptosis is crucial for preventing neonatal brain damage.
Area of Science:
- Neonatal Neurology
- Developmental Neuroscience
- Cellular Pathology
Background:
- White matter injury in preterm infants is a major cause of mortality and neurological deficits.
- The role of apoptosis in this injury remains poorly understood.
Purpose of the Study:
- To investigate if apoptosis contributes to white matter damage in premature infants with intraventricular hemorrhage (IVH) and asymmetric periventricular echogenicity (PVE).
Main Methods:
- Examined frontoparietal white matter tissue from 21 preterm infants categorized by IVH severity and ultrasound findings.
- Utilized the terminal deoxytransferase-mediated dUTD nick-end labeling (TUNEL) assay to detect DNA fragmentation indicative of apoptosis.
- Quantified cells with apoptotic morphology, including nuclear blebs and karyorrhexis.
Main Results:
- Infants with severe IVH and PVE showed significantly higher TUNEL indices compared to controls (2.75% vs. 0.84% and 0.42%).
- A greater number of white matter cells exhibited apoptotic morphology in the severe IVH group.
- Astrocytes and oligodendroglia were the primary cell types affected by apoptosis.
Conclusions:
- Apoptosis is a significant mechanism underlying white matter cellular death in preterm infants with IVH and PVE.
- Future therapeutic strategies should focus on inhibiting apoptosis to prevent neonatal brain injury.
Abstract:
White matter injury in premature infants with or without intraventricular hemorrhage (IVH) remains an important cause of neonatal mortality and neurologic morbidity. The contribution of apoptosis to the cellular death in white matter injury in the preterm infant is unclear. The objective of this study was to determine whether apoptosis contributes to the cellular death in premature infants with cranial ultrasound (US) evidence of IVH and asymmetric periventricular echogenicity (PVE). Brain tissue incorporating frontoparietal white matter was obtained from 21 infants: 6 infants with severe IVH and asymmetric PVE (grade 1V IVH) on US (group 1); 9 infants with minimal IVH or normal US who died within 21 days (group II); and 6 infants with minimal IVH or normal US who died later (group III). The presence of DNA fragmentation, typical of apoptosis, was determined using a terminal deoxytransferase-mediated dUTD nick-end labeling (TUNEL) assay. The TUNEL index for group I infants was significantly greater, i.e., 2.75 +/- 1.94% versus 0.84 +/- 0.70% for group II and 0.42 +/- 0.22 for group III infants (P = 0.004). Most cells showing reactivity had morphologic characteristics consistent with astrocytes and oligodendroglia. The number of white matter cells showing morphologic changes consistent with apoptosis, such as nuclear blebs and karyorrhexis, was also quantitated and was significantly more numerous in group I than in group II infants, i.e., 0.51 +/- 0.64% versus 0.02 +/- 0.05% (P = 0.0005), and group III infants, i.e., 0.10 +/- 0.18% (P = 0.03). These findings implicate apoptosis as a contributing mechanism for the cellular death in infants with IVH and asymmetric PVE. Strategies aimed at preventing the white matter injury will need to incorporate methods of inhibiting the ongoing process of apoptosis.
