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Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage
James P McAllister1, Maria Montserrat Guerra1, Leandro Castaneyra Ruiz1
1From the Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri (JPM, LCR, DMM, DDL); Instituto de Antomía, Histologia y Patologia, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile (MMG, EMR); Instituto de Biología Celular, Genética y Fisiología Facultad de Ciencias, Universidad de Malaga, Malaga, Spain and Instituto de Investigación Biomédica (IBIMA), Malaga, Spain (AJJ, DDP); Departments of Pediatrics, Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (DS, WD); Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (RES); and Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri (DDL).
Insights
Ventricular zone disruption is common in premature infants with intraventricular hemorrhage (IVH). This damage to the neural stem cell niche correlates with developmental age, suggesting a link to hydrocephalus development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Intraventricular hemorrhage (IVH) is a common complication in premature neonates.
- Posthemorrhagic hydrocephalus (PHH) frequently complicates IVH, leading to significant neurological morbidity.
- The role of the ventricular and subventricular zones (VZ/SVZ) in the pathogenesis of IVH and PHH is not fully understood.
Purpose of the Study:
- To investigate alterations in the VZ and SVZ in infants with IVH.
- To determine the association between VZ/SVZ changes and the development of PHH.
- To characterize the cellular and molecular changes within the VZ/SVZ following IVH.
Main Methods:
- Postmortem brain samples from 12 infants with IVH and 3 controls were analyzed.
- Histology and immunohistochemistry were used to examine neural stem cells (NSCs), neural progenitors (NPs), ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules.
- VZ/SVZ morphology and cellular composition were compared between IVH cases and controls.
Main Results:
- Controls showed normal VZ/SVZ architecture with distinct cell populations.
- IVH cases exhibited VZ/SVZ disruption, including cell loss, eruption into the ventricle, and heterotopia.
- Mature astrocytes were found in areas of VZ disruption.
- The extent of VZ disruption correlated with developmental age but not with IVH grade or location.
Conclusions:
- VZ/SVZ disruption is a consistent finding in premature neonates with IVH.
- These alterations resemble findings in congenital hydrocephalus, suggesting a common pathogenic mechanism.
- VZ/SVZ damage may contribute to the development of PHH.
Abstract:
To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.
