Microglia

Microglia constitute a small minority (about 4%–18%) of the cells found in the normal CNS, and their numbers depend on the region examined. In early studies, Cajal (1913b) included small cells that lacked prominent processes in a group of cells that he called the “third element.” He thought that some of them might originate from mesodermal elements. Del Rio Hortega modified available silver methods and clearly identified two species of small cells with different morphological characteristics. He called them oligodendroglia (described in Sect. 3) and microglia (reviewed by del Rio Hortega 1932). In light microscopic sections of mature CNS, typical microglial cells are more abundant in gray matter, have polymorphic darkly stained nuclei, and rather scanty perinuclear cytoplasm. Their processes, which vary in number, length, and thickness, are covered with fine twigs that give microglia a distinctive spiny appearance. Cells with all of these features are readily identified as microglia. But there are small cells that may resemble microglia and also have morphological characteristics of oligodendrocytes or macrophage-like cells. In early electron microscopic studies of CNS, the range of morphological appearances reported for small cells was an added source of confusion. Better preparative methods were used in subsequent studies, and in these publications a typical microglial cell had an oval or elongated nucleus with large, marginally located clumps of chromatin and cytoplasm containing prominent long profiles of granular endoplasmic reticulum and a variable number of dense polymorphic inclusions (Peters et al. 1976). However, as in light microscopic sections, there were small cells with an appearance intermediate between this and the one described for other cells. Additional problems were the lack of specific markers and the substantial regional and species differences in microglial morphologies. These problems added significantly to the uncertainties of establishing microglial identity during development. They also partially explain why less was known about the genesis of microglia than other glial types.