The microglial cell. A historical review

Effectively, modern research has confirmed Hortega's view of the origin of the microgliacyte from circulating monocytes of the monocyte-macrophage series that invade the brain during embryonic and early postnatal life. Their phagocytic capacity is exercised during the brain remodelling that marks brain maturation. They then convert to the ramified resting microglial cell visualized in the silver carbonate staining technique of Hortega and by modern lectin-binding methods. In response to injury, reactive microglia exhibit hypertrophy and hyperplasia, and may or may not go on to form typical lipid-laden phagocytes. Activated microglia show upregulation of the many marker antigens they share with circulating monocytes, including the major histocompatibility class (MHC) class II antigens that bespeak their immunocompetent nature. However, MHC class I and II expression and development of immunohistochemical positivity for cytoplasmic and plasma membrane antigens that characterize the monocyte-macrophage do not necessarily indicate an immunological response though there is ample evidence that microglia can serve as antigen-presenting cells. Rather, microglia are extraordinarily sensitive to changes in the brain microenvironment, whatever the nature of the exciting mechanism or substance. They may be considered to serve an ever alert, protective and supportive function that can be assembled rapidly to deal with infections, physical injuries, physiologic changes and systemic influences. In addition to elaboration and secretion of cytokines with varied actions, e.g., suppression of astrogliosis, they secrete factors, including nerve growth factor, which are supportive of neurons. They have an important role in iron metabolism and the storage of iron and ferritin. They may promote central nervous system regeneration. They are prominently involved in such pathologic processes as the acquired immunodeficiency syndrome, multiple sclerosis, prion diseases and the degenerative disorders, e.g., Alzheimer's disease and Parkinson's disease. With aging, they grow more numerous, become richer in iron and ferritin and exhibit phenotypic alteration, e.g., the expression of MHC class II antigens that are not ordinarily demonstrable immunohistochemically in the resting state. The rate of growth of our knowledge of microglia during the last decade has been exponential and continues.