254 Maternal Antibodies to Fetal Brain Neurons and Autism
specific progenitor cells in the developing fetal brains, resulting in develop
ment of maternal autoantibodies. This hypothesis can be examined by inject
ing fetal brain antigens into pregnant Rhesus monkeys at early gestation. Our
hypothesis may explain why a small percentage of mothers give birth to multi
ple ASD children. However, we do not discount the possibility that other anti
gens, after an infection with viral agents or microorganisms that cross react
with fetal brain antigens, may play a role in the development of ASD.Blood–Brain Barrier
What is the BBB?
In humans the CNS is protected by a complex vascularized and dense capil
lary connection that serves as a barrier against any insult from the blood
circulation. This highly sophisticated system allows the measured transport
of oxygen and essential nutrients and removes carbon dioxide and harmful
waste products. The BBB is the result of a specialized construct of blood
vessels. These blood vessels are distinguished from vasculature in other tis
sues, enabling CNS vessels to strictly regulate the delivery of cells (i.e., micro
glial cells, monocytes), molecules and ions between the circulatory system
blood and the CNS tissue (Figure 8.5). Therefore, a better understanding of
the true nature of the BBB in a developing fetus is essential in understanding
the ways a fetal brain may sustain injury from synthetic chemicals, infections,
and mechanical trauma of the woman carrying the fetus. As shown in
Figure 8.5, during fetal development many of the properties of the BBB are
possessed by the endothelial cells that form the walls of the blood vessels but
are assimilated through a series of complex cellular interactions with the
microenvironment. The BBB is not an organ but is a “neurovascular unit”
and it comprises the endothelial cells, pericytes, microglia, astrocytes, and
basement membrane that are characteristic of the cerebral vasculature
(Figure 8.5).
It is a widely believed among neuroscientists that the BBB in the embryo,
fetus, and newborn is “immature” and poorly formed. This unfortunate con
cept of a so called “‘leaky” BBB is incorrect [47] and without any scientific evi
dence; it was thoroughly examined and rebuffed by Saunders et al. [47] in their
outstanding and comprehensive review of this subject. One historical reason
for the belief in barrier immaturity comes from an early paradigm that was
established in the 1930s that the fetal brain would not need a barrier, because
the fetus is protected by a placenta (Figure 8.5). The developing brain is neces
sarily immature compared with that of the adult, but the real question should
be about the functional status of the BBB mechanisms in embryos, fetuses, and
infants, compared with adults.