Morphological forms and localization of microglial cells in the developing human cerebellum.

There are relatively few studies on microglia of human developing brain thus function and location of these cells at this period of life are unknown. Moreover, all of them concentrated on the cells in very early period of fetal life. To achieve further insight into the participation of microglial cells in the development of the central nervous system the brains of fetuses, newborns and infants were examined by means of immunological markers: Ricinus communis agglutinin-1 (RCA-1) and ferritin antiserum. Brains of 12 fetuses and infants ranging in age from 14 weeks of gestation to 5 months after birth were used in the study. The fetuses were derived following spontaneous abortions. In pre-term and term newborns the cause of death was of maternal origin (placental insufficiency) or accidental sudden death. Coronal blocks of cerebellum cut into 5 microns thick sections were used in the study. The developing microglial cells were detected by both markers (RCA-1 and anti-ferritin). Ricinus communis agglutinin recognizes carbohydrate residues on the surfaces of microglial and endothelial cells. Therefore, in the sections incubated with this lectin brain vessels as well as microglia were visualized. The second microglial marker anti-ferritin serum detected precisely all morphological subpopulations of microglia including ameboid and ramified cells but endothelial cells remained immunonegative. Therefore, in 14 weeks of gestation only round ameboid microglia were ferritin-immunopositive in cerebellum. These cells were localized at the periphery of the periventricular, germinal matrix and were surrounding a group of nerve cells of the developing dentate nucleus. In 16 week-old fetuses ameboid cells were present in the hilus and between gyri of the dentate nucleus. The ferritin-positive microglial cells on the convolutions of the dentate nucleus gyri manifested as the cells with short fine branched processes and scanty cytoplasm. In cerebellum of the 20 week-old fetuses the subpopulation of branched (ramified) microglia were more numerous than ameboid cells. Ameboid cells were present mainly in the intermediate zone of the future white matter and ramified cells penetrated the inner (at the one third of its thickness) part of the developing internal granular layer of cerebellar cortex. The upper part of cerebellar cortex was colonized by microglia between 24-28 weeks of gestation. In cerebellum of fetuses over 28 weeks of gestation numerous microglial cells infiltrated mainly the Purkinje cell layer, first in the vermis, later in the hemispheres. From 36 weeks of gestation to the birth ferritin-immunopositive microglial cells gradually disappeared from the cerebellar cortex. The microglia of the term newborns and of a 5 month-old child manifested mainly as ramified cells located in the white matter. The results of our study lead to the conclusion that the localization of microglial cells in the brain structure and their morphological forms correlate precisely with the appropriate stages of the brain development.