MESOGLIA & MICROGLIA – A Historical Review of the Concept of Mononuclear Phagocytes Within the Central Nervous System

Abstract

More than a century and a half has elapsed since the first accounts of mesodermal phagocytic elements were proposed within the central nervous system. Over the intervening decades, body and substance were added to this concept through the advancement of histological techniques at the disposal of the researcher and the acute and keen-minded skills of the pathologist. Notable among these pioneering efforts were the contributions of W. Ford Robertson, Santiago Ramon y Cajal, Pio del Rio-Hortega and Wilder Penfield amongst an entire cavalcade of other noteworthy figures. The term 'mesoglia' and 'third element of the nervous system' was bestowed upon these cells towards the beginning of the twentieth century to account for their separate origins from neurons and macroglia. It was later amended by del Rio-Hortega in 1919, to 'microglia' in order to further discriminate between true mesodermal elements and oligodendrocytes, previously regarded as a component of 'mesoglia'. This particular contention sparked much controversy among del Rio-Hortega's peers and resulted in an escalation of fruitful research throughout Europe that eventually declined up to the outbreak of the Second World War. The post-war years were a period of the 'dark ages' that cast doubt on the very existence and nature of microglia, until the 'renaissance' of research was once again rejuvenated in the 1960s, by a new cohort of intrigued minds: Cammermeyer, Blinzinger, Kreutzberg and others who saw in the 'third element' the potential that is now commonly ascribed to microglia: the intrinsic immune effector cells of the CNS. It is now universally accepted that microglia are involved as the first line of rapid defence in any pathology of the nervous system, and as such, present a diagnostic tool for the neuropathologist. Although our knowledge of microglia stems from an extensive body of work conducted over the last two decades, much of the earlier work (pre-1960s) has remained somewhat obscure. This is partly accountable due to the limited availability of translated works, and additionally to the lack of a compendium of these articles. This paper will present a comprehensive overview of the pioneering research on mononuclear phagocytes within the central nervous system, which has direct bearing on our present-day understanding of the concept of microglia.

P2X4R+ microglia drive neuropathic pain

“…Microglial proliferation, and also the stereotyped changes in morphology and in the repertoire of genes expressed, are reliably induced by damage to peripheral sensory nerves in rodent models regardless of the type of injury 13 . The microglial responses to peripheral nerve injury are induced so consistently that all schemes for pain hypersensitivity after nerve injury envisage some requisite degree of spinal microglial reactivity 13,14 .…”

“…The microglial responses to peripheral nerve injury are induced so consistently that all schemes for pain hypersensitivity after nerve injury envisage some requisite degree of spinal microglial reactivity 13,14 . In contrast, these are typically not observed in inflammatory and chemotoxic models of pain [15][16][17] , although they have been seen by some investigators.…”

Microglia in the CNS: Immigrants from another world

“…Histological data indicate that the first microglia precursors colonize the CNS during the embryonic and fetal phases of development (Rezaie and Male, 2002). The first macrophage-like cells with an ameboid shape appear in the rodent neuroepithelium as early as day 8.5-10 of embryogenesis (Ashwell, 1990(Ashwell, ,1991Chan et al, 2007) independent of a developed circulatory system (Kurz and Christ, 1998).…”

Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury

“…Microglia, the resident immune cells in the CNS, and the first myeloid cells to respond to SCI, are widely believed to be derived from circulating hematopoietic precursors, mostly blood monocytes that colonize the CNS during late stages of development [56][57][58]. However, recent data indicate that adult microglia arise instead from extra-embryonic yolk sac myeloid precursors during embryogenesis (about embryonic day 8) [31] (FIG.…”