Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone

Abstract

Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n = 18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age > 18 years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+ cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the subventricular niche as well as the width of corpus callosum and internal capsule.

The aged brain: genesis and fate of residual progenitor cells in the subventricular zone

“…It has been reported that aging gradually affects the number, size, and composition of these structures suggesting that, through their interaction with NSCs, fractons could be related to the loss of neurogenesis during aging (Kerever et al, 2015 ). According to this, changes in fractone ultrastructure have been described in an experimental obstruction model of hydrocephalus in mice, which showed decreased NSCs proliferation in the SVZ (Campos-Ordoñez et al, 2014 ). Future studies will provide a more comprehensive understanding on the function of fractones in the neurogenic niche.…”

Hydrocephalus Revisited: New Insights into Dynamics of Neurofluids on Macro- and Microscales

“…NO is also important for the structural maintenance of the periventricular subependymal zone. 77 It may therefore be worthwhile to focus on elevated NO expression in microgravity as well as in gravity simulation experiments by rat tail suspension or during human HDT. 78…”

Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage

“…Intraventricular hemorrhage (IVH) arises from rupture of immature and developing blood vessels in the germinal matrix of premature infants. IVH occurs in up to 25% of preterm neonates where 10% of events are further complicated by hydrocephalus (Campos-Ordonez et al, 2014 ; Koschnitzky et al, 2018 ). A recent NIH workshop on post-hemorrhagic hydrocephalus (PHH) reported that IVH affected neonates develop somatic growth impairment, white matter damage, motor dysfunction and neurocognitive deficiency (Koschnitzky et al, 2018 ).…”