Area Postrema: Fetal Maturation, Tumors, Vomiting Center, Growth, Role in Neuromyelitis Optica.

INTRODUCTION: The area postrema in the caudal fourth ventricular floor is highly vascular without blood-brain or blood-cerebrospinal fluid barrier. In addition to its function as vomiting center, several others are part of the circumventricular organs for vasomotor/angiotensin II regulation, role in neuromyelitis optica related to aquaporin-4, and somatic growth and appetite regulation. Functions are immature at birth. The purpose was to demonstrate neuronal, synaptic, glial, or ependymal maturation in the area postrema of normal fetuses. We describe three area postrema tumors. METHODS: Sections of caudal fourth ventricle of 12 normal human fetal brains at autopsy aged six to 40 weeks and three infants aged three to 18 months were examined. Immunocytochemical neuronal and glial markers were applied to paraffin sections. Two infants with area postrema tumors and another with neurocutaneous melanocytosis and pernicious vomiting also studied. RESULTS: Area postrema neurons exhibited cytologic maturity and synaptic circuitry by 14 weeks'. Astrocytes coexpressed vimentin, glial fibrillary acidic protein, and S-100ß protein. The ependyma is thin over area postrema, with fetal ependymocytic basal processes. A glial layer separates area postrema from medullary tegmentum. Melanocytes infiltrated area postrema in the toddler with pernicious vomiting; two children had primary area postrema pilocytic astrocytomas. CONCLUSIONS: Although area postrema is cytologically mature by 14 weeks, growth increases and functions mature during postnatal months. We recommend neuroimaging for patients with unexplained vomiting and that area postrema neuropathology includes synaptophysin and microtubule-associated protein-2 in patients with suspected dysfunction.

Area postrema undergoes dynamic postnatal changes in mice and humans.

The postnatal period in mammals represents a developmental epoch of significant change in the autonomic nervous system (ANS). This study focuses on postnatal development of the area postrema, a crucial ANS structure that regulates temperature, breathing, and satiety, among other activities. We find that the human area postrema undergoes significant developmental changes during postnatal development. To characterize these changes further, we used transgenic mouse reagents to delineate neuronal circuitry. We discovered that, although a well-formed ANS scaffold exists early in embryonic development, the area postrema shows a delayed maturation. Specifically, postnatal days 0-7 in mice show no significant change in area postrema volume or synaptic input from PHOX2B-derived neurons. In contrast, postnatal days 7-20 show a significant increase in volume and synaptic input from PHOX2B-derived neurons. We conclude that key ANS structures show unexpected dynamic developmental changes during postnatal development. These data provide a basis for understanding ANS dysfunction and disease predisposition in premature and postnatal humans.

Development of the area postrema: an immunohistochemical study in the macaque.

The organization and chemical development of the area postrema (AP) in the macaque monkey was studied by immunohistochemistry imaged with conventional and confocal microscopy from day 40 of gestation to adulthood. The thin ependyma of the adult was found to develop from a thick continuous structure beginning in the second trimester. It was later invaded by tyrosine hydroxylase immunoreactive (TH+) and dopamine beta-hydroxylase immunoreactive (DBH+) cells and fibers, suggesting a possible route for release of neurotransmitter directly into ventricular cerebrospinal fluid. Other TH+ and/or DBH+ fibers were found in close approximation to blood vessels. Prominent vascularity of the parenchyma of AP was present late in the first trimester (fetal day (Fd)57 in the macaque) and increased further until birth. By contrast, the underlying solitary nucleus was hypervascular at Fd57, but its vascularity rapidly declined by late in the second trimester. TH+ neurons first appeared late in the first trimester, and DBH+ neurons appeared in the second trimester; these findings are consistent with the view that catecholaminergic cells in AP are the earliest members of the A2 noradrenergic group. Catecholaminergic cells or fibers in AP contained little labeling for synaptic vesicular proteins, suggesting that the release of neurotransmitter there may not involve a synaptic mechanism. Synapses were first observed in mid-second trimester, and most were associated with GABA+ fibers.