title: 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.
authors.affiliation: Laboratory of Neuroscience, Facultad de Psicologia, University of Colima, Colima, COL, 28040, Mexico.
authors.forename: Tania
authors.initials: T
authors.lastname: Campos-Ordoñez
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles, University of Valencia, Valencia 46980, CIBERNED, Spain; Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe-UVEG, Valencia 46013, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Herranz-Pérez
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Kaisorn L
authors.initials: KL
authors.lastname: Chaichana
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Jordina
authors.initials: J
authors.lastname: Rincon-Torroella
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Rigamonti
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles, University of Valencia, Valencia 46980, CIBERNED, Spain; Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe-UVEG, Valencia 46013, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD 21201, USA. Electronic address: aquinon2@jhmi.edu.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
authors.affiliation: Laboratory of Neuroscience, Facultad de Psicologia, University of Colima, Colima, COL, 28040, Mexico. Electronic address: osglez@ucol.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez-Perez
mesh_terms: D000328:Adult; D000818:Animals; D015331:Cohort Studies; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006849:Hydrocephalus / Q000473:pathology* / Q000503:physiopathology; D020772:Internal Capsule / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: Aqueductal stenosis; Fractones; Human brain; Hydrocephalus; Neural stem cells; Neurogenesis; Subventricular zone