Variability of the medullary arcuate nucleus in humans

Abstract

IntroductionThe arcuate nucleus is a component of the ventral medullary surface involved in chemoreception and breathing control. The hypoplasia of this nucleus is a very frequent finding in victims of sudden unexplained fetal and infant death (from the last weeks of pregnancy to the first year of life). On the contrary, this developmental alteration is rarely present in age‐matched controls who died of defined causes. These observations lead to hypothesize that a well‐developed and functional arcuate nucleus is generally required to sustain life. The aim of this study was to investigate whether the arcuate nucleus maintains the same supposed function throughout life.MethodsWe carried out neuropathological examinations of brainstems obtained from 25 adult subjects, 18 males and 7 females, aged between 34 and 89 years, who died from various causes.ResultsFor almost half of the cases (44%) microscopic examinations of serial histological sections of medulla oblongata showed a normal cytoarchitecture of the arcuate nucleus, extending along the pyramids. For the remaining 56% of cases, various degrees of hypodevelopment of this nucleus were observed, validated through the application of quantitative morphometric investigations, from decreased area, neuron number and volume, to full aplasia.ConclusionsThese unexpected findings indicate that the involvement of the arcuate nucleus in chemoreception in adulthood is questionable, given the possibility of living until late age without this nucleus. This opens new perspectives for researchers on the role and function of the arcuate nucleus in humans from birth to old age.

Hypertrophy of the Anterior External Arcuate Fasciculus: A Rare Variant With Implications for the Development of the Arcuate Nucleus

“…Morphometric analysis of the AN showed an average crosssectional area of 1.06 and 1.15 mm 2 for the control cases and 1.01 mm 2 in the index case. This is consistent with prior findings (Paradiso et al, 2018), which measured the cross-sectional areas of the normal ANs and found average areas of 2.76 ± 0.55 and 1.06 ± 0.3 mm 2 in their cases. The medullary pyramids, which appeared to be of normal size, had cross-sectional areas of 8.23 mm 2 in the controls and 7.60 mm 2 in the index case.…”

“…In humans, fibers from the AN project both ventrally in the AEAF and dorsally to the caudal raphe and superficial ventrolateral medullary regions (Zec et al, 1997), but the cerebellar target of the human AN has not yet been fully established. The AN in humans has an average transverse area of 1-3 mm 2 (Paradiso et al, 2018).…”

Individual variability in the size and organization of the human arcuate nucleus of the medulla

“…These data suggest that the aplasia of the Arc is not the critical cause of SIDS. This interpretation is consistent with the reports that the human Arc is small or absent in a set of adult human cases (Paradiso et al 2018), and consistent with our data showing individual variability in Arc size. Furthermore, a number of studies have found other CNS abnormalities in SIDS (Ambrose et al 2018(Ambrose et al , 2019Jaster et al 2008;Kinney et al 2003; Lavezzi et al…”

“…Aplasia of the Arc would, by that interpretation, lead to respiratory failure. However, Paradiso et al (2018) found aplasia and hypoplasia of the Arc in the brains of adults, suggesting that it was not critical for survival.…”

Harmful Effect of Intrauterine Smoke Exposure on Neuronal Control of “Fetal Breathing System” in Stillbirths

“…The well-defined death causes of the 20 cases used as controls were divided into two categories: (1) abnormalities of the placenta, membranes and umbilical cord and (2) fetal pathologies (cardiomyopathies, severe renal dysplasia, pneumonia, septicemia, karyotype abnormalities). In five cases, the neuropathological examination revealed neuronal alterations in the medulla oblongata and, precisely, hypoplasia of the raphe nucleus and of the arcuate nucleus, which are defects that are mostly deemed to be compatible with life [ 16 ].…”