Expansion of the Human Embryonic Brain During Rapid Growth: Area Analysis

Abstract

This report focuses on growth of the brain of the early human embryo, Carnegie stages 12-23. Areas of median sections from 50 to 58 embryos were measured to determine the best mathematical model to describe growth of the three primary brain vesicles and to determine the change in the ratio of tissue to cavity areas (T/C). An exponential model best describes growth of the brain and head during this time period. The head expands 248-fold compared with a 171-fold growth of the brain. The whole brain, forebrain, and midbrain all exhibit larger cavities than tissue initially followed by a reversal of such at a critical time (stages 21-24). The presumptive cerebellar tissue which was twice the cavity initially grows to become more than six times the cavity. Boxplots of the T/C ratios for the head and brain plus its components reveal that initially the tissue is less than the cavity (10-20% and 40-60%, respectively) but eventually becomes larger Key words: growth parameters; brain expansion; mathematical models; CSF; cerebrospinal fluid pressure The brain and spinal cord or the central nervous system (CNS) first becomes apparent between the fourth and eighth weeks of development in the human (Desmond and O'Rahilly, 1981;O'Rahilly and Muller, 2006). Human embryology texts feature the elaborate changes in morphology that occur in the CNS during this time period but are remiss in conveying the tremendous growth of the embryonic CNS during these 4 weeks (Moore and Persaud, 2008a,b;Sadler, 2006). In fact, only one article exists in the literature to this day that documents such growth. This was a study reported more than 25 years ago by Desmond and O'Rahilly in which they measured the major axes of the three embryo brain vesicles. In that study, they compared the growth of the brain during the embryonic period, 4 to 8 weeks, with the fetal period, 8 weeks to birth. The study was limited to measuring one-dimensional lengths of the three major axes of the three embryo brain vesicles, namely, the bi-temporal (ear to ear) measurement, the frontal-occipital (forehead to back-of-head) measurement, and the dorsal-ventral (top-of-head to base) measurement. These findings, based on using one-dimensional axes, showed that the rates of growth of all three embryonic brain vesicles was much greater than the corresponding vesicles of the fetal period (Desmond and O'Rahilly, 1981).Interestingly, many of the current texts of human embryology draw attention to some of the more prominent abnormalities of the central nervous system such as hydrocephalus, spina bifida, and the Chiari type II malformation (Moore and Persaud, 2008a,b;Sadler, 2006). These same texts make no mention of the growth of the CNS and how mechanisms of growth might well play a role in these malformations.

Morphology and morphometry of the human embryonic brain: A three-dimensional analysis

“…Levitan and Desmond (2009) previously noted that an increase in the volumes of the brain cavities is a feature of the embryonic period. The cavity volume was relatively large, but there was no exponential increase in cavity volume, despite the complicated changes that the cavity underwent in the late embryonic stages in our study.…”

“…The present study showed that the morphology of both the brain tissue and cavity of the rhombencephalon was affected by the development of the pons and medulla of the brain stem and the cerebellum according to their respective growth time lines. Previous studies have suggested that morphometric changes of the rhombencephalon differ from the other vesicles (Desmond and O'Rahilly, 1981;Levitan and Desmond, 2009). In our study, growth of the brain stem was apparent until CS17, prior to detectable growth of the cerebellum.…”

“…With regard to the embryonic period proper, Desmond and O'Rahilly (1981) measured the major axes of the three embryonic brain vesicles and showed that the rates of growth of all three embryonic brain vesicles were much greater than the growth of the corresponding vesicles during the fetal period. Levitan and Desmond (2009) measured the areas of median sections two dimensionally to describe the growth of the three primary brain vesicles and to determine the change in the ratio of tissue area to cavity area. These studies were not able to accurately reconstruct the growth of the brain, region by region.…”

Morphometric human embryonic brain features according to developmental stage

“…Morphometrical studies (both 2D and 3D) can be analyzed using serial histological sections and visualized via 3D modeling and illustrations . However, these methods are laborious and inaccurate.…”

The Longitudinal Growth of the Neuromeres and the Resulting Brain in the Human Embryo

“…The neuromeres considered individually, however, were not a part of that study, nor were the complexities of the telencephalon, and the definitions of segments measured are in need of much greater precision. In a subsequent article on areas [Levitan and Desmond, 2009], but based on the 1981 data, mathematical analysis is vitiated by erroneous morphology and incorrect boundaries. It is important to emphasize that revision is necessary for studies of the embryonic period made before the era of systematic, precise graphic reconstructions of the brain at each stage, which began in the 1980s [references in O'Rahilly and Müller, 2006, table 23-2].…”