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Ultrastructural, three-dimensional reconstruction of cells surrounding the amyloid star in classical plaques in Alzheimer’s disease (AD) were carried out to determine the cells associated with the deposits of beta-protein amyloid fibrils. These studies showed that the amyloid fibrils appear first within the altered cisternae of endoplasmic reticulum (ER) and infoldings of plasma membranes of microglia/macrophages further supporting our conclusion that the microglia/macrophages are the site of formation of amyloid fibrils.p ]

This chapter will focus on aging in the nonhuman primate cerebral cortex. Essentially the review documents what is known about aging changes in the cerebral cortex of the rhesus monkey, Macaca mulatta, since this is the species that has been most extensively used in such studies. But before the existing information is reviewed, it is appropriate to consider what is known about the life span of this species, so that we can define the period of the life span when a rhesus monkey can be considered to be old.

An approximate twofold increase in microglial cell densities occurred in the hypoglossal and dorsal motor vagal nuclei of the cat after transection of their respective nerves. The densities of astrocytes and oligodendrocytes were unaffected. A significant loss of neurons was demonstrated in both nuclei. These findings indicate that a perineuronal microglial cell reaction occurs in craniomotor nuclei of the cat following nerve transection, but to a considerably lesser extent than in rats and rabbits. We suggest that the different glial response after nerve transection compared with nerve crush in the cat may be related to differences in the degree of axotomy-induced neuronal degeneration.

The author studied the ultrastructural characteristics of the microglial cell in the cerebral cortex of the adult rat and rabbit, admitting the identity and independence of this glial type in relation to the other cells of the nervous tissue. He also discussed the microglial nature of the pericytes ("pericytial microglia").

Microglial cells are absent from the corpus callosum of newborn rats. In the hope of finding out when and how microglial cells appear with age, 3H-thymidine was given intraperitoneally as single or three shortly spaced injections to 5-day-old rats weighing about 15 g; and these animals were sacrificed at various time intervals from 2 hours to 35 days later. Pieces of corpus callosum were taken near the superior lateral angle of the lateral ventricles; and semithin sections were radioautographed and stained with toluidine blue. The corpus callosum of 5-day-old rats is composed of loosely arranged unmyelinated fibers and scattered cells. Among these cells, microglia are rare; there are a few astrocytes, many immature glial cells, rare pericytes, and 6-7% of phagocytic “ameboid cells” consisting of a few monocytes and many macrophages. In the animals sacrificed two hours after 3H-thymidine administration, label is present only in immature cells and “ameboid cells.” As time elapses and the fibers of corpus callosum become myelinated, oligodendrocytes and, later, microglial cells appear. At the age of 12 days, microglial cells are present in substantial number; and by 19 days, the number doubles to reach a plateau. Many of the new microglial cells are labeled, e.g., 78.1% in 12-day-old animals (7 days after 3H-thymidine administration). The labeled microglial cells must have come from the transformation of cells that acquired label early, that is, from the immature cells or the “ameboid cells.” The height of the peaks of labeling – 59.8% at nine days for immature cells and 77.8% at 12 days for “ameboid cells” – points to the latter as precursors of the highly labeled microglial cells. Furthermore, the “ameboid cells” disappear as microglial cells appear and there are transitional elements between these two cell types. Cell counts suggest that about a third of the “ameboid cells” transform into microglial cells, while the others degenerate and die. Thus, the microglial cells which appear in the corpus callosum during the first three weeks of life result from transformation of the “ameboid cells” – a group of macrophages showing various stages of transition from monocytes. As for the occasional microglial cell appearing after the third week or in the adult, they presumably come directly from monocytes. In either case, monocytes would be the intial precursors.

Although gliomas of the optic nerve are oligodendroglial cells in the nerve stem. The relatively uncommon, they occur frequently enough to consider them in every case of proptosis of the globe. A study of these tumors in the registry of the Armed Forces Institute of Pathology re­ veals occurrences of 18 per 50 thousand. At Walter Reed Army Hospital, in-patient and out-patient lists show about one third of this incidence for all ages of individuals seeking ophthalmic examination and care. Observa­ tions show glioma to be a disease of puberty, the average age being from 10 to 12 years. The youngest patient was seven months old, while the oldest was 47 years. Ingalls, how­ ever, reports glioma to be a disease of in­ fancy while Katzin agrees with our observa­ tion. Discussion of the disease would be in­ complete without a review of the histoanatomic structure of the optic nerve which is unlike peripheral nerve. It is similar in architecture to the cerebral pathways except for the presence of vasculofibrous septa which divide the nerve into bundles. The nerve fibers are further separated by glial network, the cells of which resemble those found in the central nervous system. These cells are the astrocyte, the oligodendrocyte, and the microglial cell. The tumor may grow from any one of these cells. The dominant cell is usually the astrocyte. However, many specimens show an equal distribution of astrocytes and oligodendrocytes. According to Davis these cells may develop tumors which may be described in five different stages. There may be a gen­ eralized hyperplasia of the astrocytes and the

Intraventricular macrophages are first seen attached to the presumptive choroid plexus in the 11 days postconception mouse. By 12 days postconception supraependy- ma1 macrophages are present as well as a few macrophages lying apparently free within the ventricles. The number of epiplexus, supraependymal and free macro- phages increases rapidly and reaches a peak at 17 days postconception, then fall rapidly until 4 days post natum. A second increase in epiplexus and supraependymal cells occurs at 8 days post natum followed by another decrease up to 15 days post natum. Microglia were first observed in the brain at 13 days postconception and at 17 days postconception a microglial cell was observed apparently entering the ependyma from the ventricle. It is suggested that the large decrease in intraventricular macrophages after 17 days postconception is due to many of these cells migrating into the brain to give rise to microglia. The intraventricular macrophages them- selves probably arise from within the choroid plexus, either from stromal cells or from blood-borne macrophages.

An antiserum-specific for mesodermal cells with cross-reactivity with microglia has been prepared by immunizing rabbits with unstimulated rat peritoneal macrophages. The characteristics of the antigens and antiserum are presented. The anti-macrophage antiserum provides one way of positive identification of reactive mesodermal macrophages of a monocytic origin both in nervous tissue and in cerebrospinal fluid.

Astrocytes are easily identified by means of their lightly stained nuclei with a distinct outline which contrasts with the light cytoplasm (Fig. 3). The nuclei (9-12 × 5-9 μm) of the astrocytes within the upper regions of the cortex show homogeneously distributed chromatin, whereas those in the deeper layers frequently display small heterochromatin clumps. This is probably due to ischemic changes during surgical and fixation procedures (Jenkins et al. 1979). A different vulnerability of astrocytes within different layers should also be taken into account. In the vicinity of the nucleus. greenish-yellow-stained pigment inclusions occur.

The origin, structure and function of microglial cells are among the most controversial subjects in neurocytology. On the basis of extensive histological and experimental data del Rio Hortega (1919, 1932) (17, 18) developed the classical concept of microglia, proposing their mesodermal origin and their function as brain macrophages. Since then this concept has been confirmed as well as challenged and the vast literature reflects this controversy (for reviews see 19, 5, 16, 8, 1, 12, 14, 15, 6).

As mentioned above, the question has recently been raised as to whether or not extra-vascularly located, so-called mononuclear phagocytes (MP) are present in the central nervous system (CNS) and/or the peripheral nervous system (PNS). In order to approach the problem, the current situation in which the question has developed is discussed; the morphologic studies conducted in the past which interpreted the problem similarly are summarized, Finally, on the basis of the available literature a synopsis of the classification of a series of highly active phagocytic cells in the CNS is presented. Unfortunately, a certain amount of repetition could not be avoided in working through the relevant literature under these various aspects.

Following special impregnation methods, microglia, mesoglia, or Hortega cells (Figs. A1, B1), appear in all regions of the CNS, predominantly however near capillaries. Irregular, sometimes bushlike processes extend from the long cell body (Fig. A).

The present chapter deals with the periods during pre- and postnatal ontogeny in which the individual cell types or their direct precursors are capable of proliferation. The degree of proliferation, i.e., the question of how many cells of a particular type are proliferating, will not be discussed here.