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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Damage to the choroid plexus, ependyma and subependyma as a consequence of perinatal hypoxia/ischemia
Raymond P Rothstein1, Steven W Levison
1Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa 17033, USA.
Insights
Perinatal hypoxic-ischemic (H/I) brain injury affects premature infants. This study reveals the choroid plexus is highly vulnerable, while neural stem cells in the subventricular zone show resistance to H/I damage.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Medicine
Background:
- Cerebral hypoxia/ischemia (H/I) in premature infants is a leading cause of cerebral palsy and cognitive impairment.
- The vulnerability of brain stem cells and progenitors to H/I injury significantly impacts neurodevelopmental outcomes.
- Understanding cell-specific responses to H/I is crucial for developing targeted neuroprotective strategies.
Purpose of the Study:
- To identify the most vulnerable cell populations in the periventricular region during early recovery from perinatal H/I.
- To investigate the differential susceptibility of various cell types, including stem cells, to H/I insult.
Main Methods:
- Analysis of brain tissue at 0 hours post-recovery from a perinatal H/I insult model.
- Histological examination to assess cell damage, including necrosis, apoptosis, and swelling.
- Identification of cell types and their responses using markers for macrophages/microglia.
Main Results:
- The choroid plexus exhibited extensive necrotic damage immediately after H/I.
- Ependymal and medial subependymal cells showed swelling but limited permanent damage.
- Lateral subventricular zone cells underwent delayed but significant apoptotic and hybrid cell death, with activated microglia involvement.
Conclusions:
- The choroid plexus is a highly vulnerable structure in the immature brain following H/I.
- Ependymal and adjacent subependymal cells demonstrate relative resistance to perinatal H/I.
- Neural stem cells within the medial subventricular zone are predicted to be resistant to perinatal H/I brain damage.
Abstract:
Cerebral hypoxia/ischemia (H/I) of the premature infant is a major cause of cerebral palsy and mental retardation. An important determinant of the ultimate outcome from this insult is the extent to which the stem cells and progenitors in the brain are affected. Irreversible injury to these cells will impair normal development of the infant's brain and, hence, its function. In the present study, we examine early intervals after H/I to identify which cells in the periventricular region are most vulnerable. At 0 h of recovery from a perinatal H/I insult, the choroid plexus shows extensive necrotic damage. The adjacent ependymal and subependymal cells are also affected. Swelling of the ependymal and medial subependymal cells is observed; however, these cells rarely sustain permanent damage. By contrast, cells in the most lateral aspect of the subventricular zone (SVZ) show more delayed, but extensive apoptotic and hybrid cell deaths. Interestingly, activated macrophages/microglia are observed adjacent to the swollen ependymal cells as well as within the affected subependyma. We conclude that the choroid plexus is an especially vulnerable structure in the immature brain, whereas the ependymal and adjacent subependymal cells are relatively resistant to damage. As the medial aspect of the SVZ contains neural stem cells, we predict that neural stem cells will be especially resistant to perinatal H/I brain damage.
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