Pharyngo-esophageal motility reflex mechanisms in the human neonate: Importance of integrative cross-systems physiology

Swallowing is a critical function for survival and development in human neonates, and requires cross-system coordination between neurologic, airway, and digestive motility systems. Development of pharyngo-esophageal motility is influenced by intra- and extra-uterine development, pregnancy complications, and neonatal comorbidities. Primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biologic conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiologic and pathophysiologic neonatal aerodigestive functions.

Apoptotic Markers in the Midbrain of the Human Neonate After Perinatal Hypoxic/Ischemic Injury

Our previous postmortem studies on neonates with neuropathological injury of perinatal hypoxia/ischemia (PHI) showed a dramatic reduction of tyrosine hydroxylase expression (dopamine synthesis enzyme) in substantia nigra (SN) neurons, with reduction of their cellular size. In order to investigate if the above observations represent an early stage of SN degeneration, we immunohistochemically studied the expression of cleaved caspase-3 (CCP3), apoptosis inducing factor (AIF), and DNA fragmentation by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin 3′-end-labeling (TUNEL) technique in the SN of 22 autopsied neonates (corrected age ranging from 34 to 46.5 gestational weeks), in relation to the severity/duration of PHI injury, as estimated by neuropathological criteria. No CCP3-immunoreactive neurons and a limited number of apoptotic TUNEL-positive neurons with pyknotic characteristics were found in the SN. Nuclear AIF staining was revealed only in few SN neurons, indicating the presence of early signs of AIF-mediated degeneration. By contrast, motor neurons of the oculomotor nucleus showed higher cytoplasmic AIF expression and nuclear translocation, possibly attributed to the combined effect of developmental processes and increased oxidative stress induced by antemortem and postmortem factors. Our study indicates the activation of AIF, but not CCP3, in the SN and oculomotor nucleus of the human neonate in the developmentally critical perinatal period.

Morphometrical Study of human neonatal cerebral cortex (Age of 28 day)

The character and timing of gyral and sulci development is one manifestation of the complex orchestration of human brain development. This work describes the morphometry and thickness measurement of human neonate cerebral cortex at age of 28 days. Four Brains samples were fixed in 10% neutral buffer formalin for 24 hrs. Slides from various brain regions were prepared and routine hamatoxylin and eosine staining procedure was applied using histological technique. The present results clarify that the brain mean measurement from the frontal to the occipital pole was 189.6 mm, while the measurements of the frontal, parietal, temporal and occipital cortices were 4.06, 3.84, 3.48 and 3.68 mm, respectively.

The Obstetrical Dilemma

An evolutionary tradeoff: bipedalism requires a narrow pelvis, but larger brains require wider birth canals. Hence early birth. Chase Nelson analyzes a new theory in the debate over human neonate helplessness. Helplessness itself exerts a selective force; it requires intelligent parents.

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

We have previously shown that perinatal hypoxic/ischemic injury (HII) may cause selective vulnerability of the mesencephalic dopaminergic neurons of human neonate. In the present study, we investigated the effect of perinatal HII on the noradrenergic neurons of the locus coeruleus (LC) of the same sample. We studied immunohistochemically the expression of tyrosine hydroxylase (TH, first limiting enzyme for catecholamine synthesis) in LC neurons of 15 autopsied infants (brains collected from the Greek Brain Bank) in relation to the neuropathological changes of acute or chronic HII of the neonatal brain. Our results showed that perinatal HII appears to affect the expression of TH and the size of LC neurons of the human neonate. In subjects with neuropathological lesions consistent with abrupt/severe HII, intense TH immunoreactivity was found in almost all neurons of the LC. In most of the neonates with neuropathological changes of prolonged or older injury, however, reduction in cell size and a decrease or absence of TH staining were observed in the LC. Intense TH immunoreactivity was found in the LC of 3 infants of the latter group, who interestingly had a longer survival time and had been treated with anticonvulsant drugs. Based on our observations and in view of experimental evidence indicating that the reduction of TH-immunoreactive neurons occurring in the LC after perinatal hypoxic insults persists into adulthood, we suggest that a dysregulation of monoaminergic neurotransmission in critical periods of brain development in humans is likely to predispose the survivors of perinatal HII, in combination with genetic susceptibility, to psychiatric and/or neurological disorders later in life.