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significant variation in phagocytic capacity between from brains of different developmental ages show
early embryo and both late embryo and neonates in distinctive trends in morphology. Many of them retain
phagocytic potential or oxidative burst in normal spine bearing surfaces that radiate from the cell body, a
condition. But the difference between late embryo feature also seen in micrographs of isolated cells. A few
and neonates is insignificant. In contrast, there is a cells remain amoeboid in shape with a ruffled surface
significant difference in phagocytosis between these membrane and short stubby projections. Ramified or
two groups (late embryo and neonates) with the adult. “resting” microglia with extended pseudopodia, isolated
Thus, it shows the trend of high phagocytic capacity just from adult brains, were also found, which in turn
before and after birth, while early adulthood microglial gives us information about the amoeboid to ramified
cells become inactive in terms of phagocytosis, therefore, transition throughout the various developmental phases
transformed into a resting or surveillance stage. or ages. [32,33] With the maturation from embryo to adult,
the shift from amoeboid to ramified morphology, is
DISCUSSION supported prominently in the silver-gold and SEM
studies. The microglia/macrophage specific CD11b
Our present study revealed a shift of microglial marker expression, determined by immunofluorescence,
structure, distribution, and function across pre- in isolated cells confirms their lineage. Phagocytosis of
and postnatal stages of development in the rat brain ultrafine carbon particles by isolated monocytic/myeloid-
under normal physiology. This transverse analysis of lineage cells occurred at all stages, from early embryo to
microglial activities in brains from embryos to adults adult, but the efficacy varied among the different groups.
shows that microglia are capable of dynamically The concept of a microglial dichotomy with M1 and M2
adjusting their position, shape, and function as the phenotypes may be examined with this model. The
[34]
developmental requirements of the CNS change. If an NBT assay, for estimating ROS generation, documented
age related structure-function model of microglia has mild phagocytic activity in the early embryo and adult
been determined, deviations from it may be diagnostic and much higher phagocytic activity in late embryos
for some CNS disorders. However, this study is limited and neonates. This difference of phagocytic activity
to the developmental maturation of the rat brain, mostly during the perinatal period is functionally related with
up to young adulthood, which excludes the aging brain. the developmental organization of brain tissue. In that
stage, neuronal positioning and extension, formation of
Our study shows significant differences in the neuronal circuitry, abrogation of wrong connections and
morphology of microglial cells throughout the reformation of proper contacts, and synaptic pruning are
developmental/age phases, along with their functional at their highest levels to develop a properly functional
attributes. Initially, by HE staining, round shaped CNS system. [13,15,35,36] Thus, there are enough phagocytic
macrophage/myeloid lineage cells, in both embryonic activities to trim and clean the forming CNS during the
and infant stages, were found in brain parenchyma, perinatal phase. [12,35,37] Furthermore, phagocytosis at
whereas in adults, these cells showed conversion into a controlled pace has an active and important role in
elongated structures. Throughout the developing brain developing and maintaining proper organization and
parenchyma, a particular colonizing pattern of blood- integrity of CNS tissue for the lifetime of the animal.
borne myeloid cells was observed as they migrated Hence, our study showed that the functionally linked
from the inner ventricular margin to the outer cortex increase in levels of basal phagocytic activity in
region. In late embryonic and infant stages, few cells microglial cells isolated from brains, before and after
were observed to enter the brain from blood vascular birth, were present mostly in cells showing an amoeboid
fenestrations. However, in adults, normal HE staining morphology. The overall information gathered from our
revealed the presence of monocytes, many of which were study is a morphological, functional relationship of
present at the margin and tethered to the endothelium, brain macrophage/microglia in normally developing rat
in the perivascular space infiltrating from the capillary brains with a significant pattern of colonization in both
into deep brain parenchyma. Thus, while transitioning early and late embryo, neonates, and even in adults.
to adulthood, cells of the myeloid lineage stabilize their This study documents the spacio-temporal activities of
positions in the CNS and develop their morphological versatile, immune-competent brain cell sunder normal
attributes. Furthermore, although the general notion physiological conditions from development to maturity.
of microglial populations being fixed in normal adult These baseline activities may be used as a reference
brains, [7,8,30,31] the present micrographs indicate a frame for detecting and analysing morphological,
potential avenue for blood-borne, myeloid-monocytic functional anomalies of microglia in deformities and
cells to enter the brain parenchyma. disease.

Ultrastructural study by SEM of isolated cells also In summary, our results show an age-dependent
revealed the structural changes. Microglia recovered variation of morphological and behavioural functioning

46 Neuroimmunol Neuroinflammation | Volume 3 | Issue 2 | February 15, 2016