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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>18years), 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.

SUBMITTER: Campos-Ordonez T

PROVIDER: S-EPMC4194226 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Campos-Ordoñez Tania T Herranz-Pérez Vicente V Chaichana Kaisorn L KL Rincon-Torroella Jordina J Rigamonti Daniele D García-Verdugo Jose M JM Quiñones-Hinojosa Alfredo A Gonzalez-Perez Oscar O

Experimental neurology 20140521

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 t ...[more]

PMID: 24858805

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Project description:BACKGROUND:Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes. OBJECTIVE:To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients. METHODS:Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). RESULTS:Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact-but not ventricular entry-associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted. CONCLUSION:SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.

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

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

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