Table 1.
Summary of the quantification of the morphological alterations observed after intraventricular administration of DMSO and the proteasome inhibitors.
Fig 1.
Partial occlusion of the rat lateral ventricle 2 weeks after administering the studied substances.
Macroscopic view of the morphological changes within the right lateral ventricle of the rat using serial coronal sections of the rats’ brains at 2 weeks after the administration of the studied substances—DMSO, MG-132, lactacystin and epoxomicin. The arrows indicate the adhesion between the ventricular walls. Staining—Nissl method; scale bar = 2 mm.
Fig 2.
Partial occlusion of the rat lateral ventricle 8 weeks after administering the studied substances.
Macroscopic view of the morphological changes within the right lateral ventricle of the rat using serial coronal sections of the rats’ brains at 8 weeks after the administration of the studied substances—DMSO, MG-132, lactacystin and epoxomicin. The arrows indicate the adhesion between the ventricular walls. Staining—Nissl method; scale bar = 2 mm.
Fig 3.
The characteristics of the ependymal discontinuity after intraventricular proteasome inhibitor administration.
Microscopic view of the different degrees of ependymal discontinuity: (A) mild, (B) moderate, (C) high on the surface of the septum, and (D) high on the surface of the corpus callosum. (E) Normal control with an unchanged ventricular ependymal lining from the same section as (D), but from the opposite side. The arrows indicate the borders between the area of the ependymal discontinuity and the existing ependymal lining. The sections were from the the rat brains at 2 weeks after administration of: A—DMSO; B, C—MG-132; and D, E—epoxomicin. Staining—Nissl method; scale bar = 100 μm.
Fig 4.
Morphological hallmarks of apoptosis and subependymal gliosis after intraventricular proteasome inhibitor administration.
Apoptotic bodies (encircled) and glial tubercles (arrow) were present in the ependymal lining of the striatum (Str) 2 weeks after MG-132 (A) and epoxomicin (B, C) administration into the right lateral ventricle (LV). Staining—Nissl method; scale bars: A, B—25 μm; C—50 μm.
Fig 5.
The characteristics of the ependymal discontinuity after epoxomicin administration.
Microscopic view of the ependymal atrophy on the surface of the corpus callosum (A). (B) Normal control with an unchanged ventricular ependymal lining from the same section as (A), but from opposite side. The arrows indicate the borders between area of the ependymal atrophy and the existing normal ependymal lining. Sections of the rat brains at 8 weeks after epoxomicin administration are shown. Staining—Nissl method; scale bar = 50 μm.
Fig 6.
The morphology of the ependymal rosettes.
Microscopic view of the ependymal rosettes formed at the ventral part of right lateral ventricle. Sections of the rat brains at 8 weeks after the administration of the studied substances are shown: A—DMSO, B—MG-132, and C—epoxomicin. Staining—Nissl method; scale bar = 100 μm.
Fig 7.
Evolution of the morphological changes within the rat lateral ventricle at 2 and 8 weeks after the administration of the studied substances.
Microscopic view of the morphological changes (glial scar, mononuclear cells infiltration) associated with the adhesion area within lateral ventricle; a comparison of the view from coronal sections of the brains from the representative rats at 2 and 8 weeks after the administration of the studied substances– DMSO, MG-132, lactacystin and epoxomicin. Staining—Nissl method; scale bar = 100 μm.
Fig 8.
Glial scar formation in the lateral ventricle.
Glial activation in the striatum (Str) and glial scar formation 2 weeks after the administration of DMSO (A) and epoxomicin (B) into the right lateral ventricle (LV). An anti-GFAP antibody was used as a marker of astroglia, an anti-NogoA antibody was used as a marker of oligodendroglia, and Neuro Trace Red stained the neuronal bodies and nuclei of both the vascular endothelial cells and glial cells. Scale bar—50 μm.
Fig 9.
The characteristics of the mononuclear cell infiltrations after intraventricular proteasome inhibitor administration.
Microscopic view of the mononuclear inflammatory cells observed at the lateral ventricular surface (A) and the different degrees of inflammatory cell infiltration: B—mild, C—moderate, and D—high. Sections of the rat brains at 2 weeks after the administration of the studied substances, A –DMSO, B, C—MG-132 and D—epoxomicin, are shown. Staining—Nissl method; scale bar = 50 μm.
Fig 10.
Microglia infiltrations within the walls of the lateral ventricle.
The OX-42-positive cells (microglia) present within inflammatory cell infiltrations are shown in sections of the rat brains at 2 weeks after the administration of the studied substances: A—DMSO, B—MG-132, C—lactacystin and D—epoxomicin. Immunohistochemistry, scale bar = 50 μm.
Fig 11.
The morphology of the ubiquitin-positive aggregates in the lateral ventricular walls and subventricular area after the proteasome inhibitor treatment.
The morphology of the ubiquitin-positive aggregates in the cells of the striatum at 2 weeks after the administration of the proteasome inhibitors into lateral ventricle is shown: A—single, small juxtanuclear aggregates (arrowhead), B—numerous larger cytoplasmic aggregates (arrowheads), and C—numerous cytoplasmic aggregates (arrowheads) and large clusters of ubiquitin-positive aggregates with a foamy morphology (arrows), which may provide the content of the phagocytic cells. Immunohistochemistry, scale bar = 50 μm.
Fig 12.
The ubiquitin-positive aggregates within the cells of subventricular area.
The localization of the ubiquitin-positive aggregates in the cells of striatum after the administration of A—DMSO and B, C—epoxomicin is shown. The arrow points to the clusters of ubiquitin-positive aggregates in astrocytes, while the arrowheads indicate small ubiquitin inclusions in cells that are not astrocytes. Scale bars: A, B—50 μm; C—25 μm.