Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells

Abstract

The lateral wall of the lateral ventricle in the human brain contains neural stem cells throughout adult life. We conducted a cytoarchitectural and ultrastructural study in complete postmortem brains (n = 7) and in postmortem (n = 42) and intraoperative tissue (n = 43) samples of the lateral walls of the human lateral ventricles. With varying thickness and cell densities, four layers were observed throughout the lateral ventricular wall: a monolayer of ependymal cells (Layer I), a hypocellular gap (Layer II), a ribbon of cells (Layer III) composed of astrocytes, and a transitional zone (Layer IV) into the brain parenchyma. Unlike rodents and nonhuman primates, adult human glial fibrillary acidic protein (GFAP)+ subventricular zone (SVZ) astrocytes are separated from the ependyma by the hypocellular gap. Some astrocytes as well as a few GFAP-cells in Layer II in the SVZ of the anterior horn and the body of the lateral ventricle appear to proliferate based on proliferating cell nuclear antigen (PCNA) and Ki67 staining. However, compared to rodents, the adult human SVZ appears to be devoid of chain migration or large numbers of newly formed young neurons. It was only in the anterior SVZ that we found examples of elongated Tuj1+ cells with migratory morphology. We provide ultrastructural criteria to identify the different cells types in the human SVZ including three distinct types of astrocytes and a group of displaced ependymal cells between Layers II and III. Ultrastructural analysis of this layer revealed a remarkable network of astrocytic and ependymal processes. This work provides a basic description of the organization of the adult human SVZ.