Journal
FLUIDS AND BARRIERS OF THE CNS
Volume 19, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12987-022-00313-3
Keywords
Kaolin-induced hydrocephalus; Pig model; Ventriculomegaly; Subventricular zone reduction; White matter alteration; Neuroinflammation
Categories
Funding
- NIH [5R21NS111249-02]
- Brusky Center for Human Immunology and Immunotherapy Programs at Washington University, Immunomonitoring Laboratory
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This study induced hydrocephalus in a pig model and found increased cell death in the periventricular white matter, decreased cell proliferation in the subventricular zone, and the occurrence of neuroinflammation.
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.
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