PMC

SVZ niche immnunostained with anti-Ki67 (green) and anti-DCX (red) antibodies in a control (A) and a 60-d hydrocephalic mouse (B). C: In the control group, the number of proliferative cells (Ki67+) and neuroblasts (DCX+ cells) was significantly higher than the 60-d hydrocephalic group (n = 5 animals per group). D: Schematic coronal sections used for quantification. Nuclei were stained with DAPI (blue). LV: Lateral ventricle; CC: Corpus callosum. * P < 0.05; Mann-Whitney “U” test. Bar = 30 μm.

Hydrocephalus model in the adult mice (A). On the top, schemes of axial, coronal and sagittal sections of the mouse brain are shown. Hydrocephalus was induced by placing a cellulose acetate film (3.0 mm length, 0.5 mm width and 0.1 mm thick) into the atrium of the aqueduct (−2.6 mm, 0 mm; anterior-posterior and lateral coordinates from Bregma, respectively) in mice. Phase-contrast imaging of the lateral ventricles of control (B) and hydrocephalus animals (C). Significant ventricular enlargement is observed 60 days after surgery (D). The average area of the ventricles was measured in >10 coronal sections taken every 200 μm (n = 5 animals per group). The graph indicates that the hydrocephalic group showed statistically significant differences when compared to controls. * P < 0.05; Mann-Whitney “U” test. Bar = 200 μm.

Morris water maze was used to evaluate cognitive impairments. Throughout the study, no statistically significant differences were observed between the groups to find the escape platform (A). Schematic coronal sections used for quantification (B). GFAP immunostaining shows reactive astrocytes along the lateral ventricles (LV) in the control and the 60-d hydrocephalus group (C). The difference in the number of astrocytes along the ventricular wall was statistically significant between animals with long-lasting hydrocephalus (n = 5 animals per group) and control animals (D). Electron microscopy confirmed the absence of astrocyte hypertrophy after induced hydrocephalus (E). The inset (F) shows a detail of a fractone with ependyma to the right and astrocytic expansions to the left. Intermediate filaments (arrowhead) are not increased as compared to the control group. Str: Striatum; LV: Lateral ventricle; bv: blood vessel; e: ependymal cells; b: astrocytes. * P < 0.05; Mann-Whitney “U” test. Bars: C = 50 μm, E = 2 μm; F = 500 nm.

The SVZ of a control mouse shows its characteristic organization in several cell layers (A). Mitotic cells (arrowhead) are frequent. Conversely, in the 60-d hydrocephalus group, the SVZ had a significant reduction in both the width and number of proliferating cells (B). Consistent chains of migrating neuroblasts (A-type cells, arrows) are seen along the SVZ in the control group (C), while the SVZ of 60-d hydrocephalic mice primarily contain an ependymal cell layer and astrocytes. Nevertheless, all cell types (A-, B- and C-type cells) are conserved and small chains of migrating cells appear scattered throughout the ventricular wall in the hydrocephalus group (D). The ependymal cell layer is often narrowed in the hydrocephalus group (E, arrows) and there are numerous fractones, which are arranged along the cells lining the walls of the ventricle when compared to control animals (F–G, asterisks). Deep interdigitations (white arrowheads) connecting with fractones (asterisks) stand out in the ependymal layer in this hydrocephalus group (H). A and B are toluidine blue-stained semithin sections and C–H are transmission electron microscopy (TEM) images. LV: Lateral ventricle; cp: choroid plexus; bv: blood vessel; a: A-type cell; b: B-type cell; c: C-type cell; e: ependymal cell. Scale bar = A, B, 10 μm; C–E, 2 μm; F–H, 500 nm.

Impact of hydrocephalus from aqueductal stenosis (AS) on the ventricular-subventricular zone (SVZ), corpus callosum, and internal capsule size in humans. Axial T2-weighted brain magnetic resonance image (MRI) and magnified T2 MRI of the SVZ (yellow line), corpus callosum (blue line), and internal capsule (green line) in a 44-year old female patient with AS due to idiopathic narrowing of the aqueduct that demonstrates the absence of pulsatile flow through the aqueduct as detected on MRI constructive interface in steady state (CISS). (A – B), a corresponding 43 year-old, female patient without AS who underwent an MRI for evaluation of headaches (D – E). Intraoperative photograph, as seen from a top view when going through the foramen of Monro, from the , demonstrating stenosis of the cerebral aqueduct (white arrow), as well as the presence of mammillary bodies (yellow arrow), thalamus (blue arrow), and floor of the third ventricle (green arrow) from the patient featured in panels A and B. (C) The widths of the SVZ (1.24 ± 0.51 vs. 2.20 ± 0.43, p<0.0001) (F) corpus callosum (3.05 ± 1.76 vs. 8.13 ± 3.44, p<0.0001) (G), and internal capsule (4.50 ± 1.90 vs. 5.43 ± 1.83, p = 0.006) (H) in patients with AS were significantly smaller as compared to age and gender-matched patients without AS.