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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2022

Open Access 01-12-2022 | Hydrocephalus | Research

Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter

Authors: Maria Garcia-Bonilla, Leandro Castaneyra-Ruiz, Sarah Zwick, Michael Talcott, Ayodamola Otun, Albert M. Isaacs, Diego M. Morales, David D. Limbrick Jr., James P. McAllister II

Published in: Fluids and Barriers of the CNS | Issue 1/2022

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Abstract

Background

Hydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants.

Methods

Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF.

Results

The expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF.

Conclusion

The induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.
Appendix
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Metadata
Title
Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter
Authors
Maria Garcia-Bonilla
Leandro Castaneyra-Ruiz
Sarah Zwick
Michael Talcott
Ayodamola Otun
Albert M. Isaacs
Diego M. Morales
David D. Limbrick Jr.
James P. McAllister II
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2022
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-022-00313-3

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