Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Development of the Hypothalamus-Pituitary-Adrenal Axis in the Fetus

Introduction The development of the hypothalamus-pituitary-adrenal (HPA) axis begins early in gestation. Corticotropin-releasing hormone (CRH) is synthesized and secreted into the hypophyseal portal circulation by the paraventricular nucleus of the hypothalamus. CRH acts on corticotroph cells in the anterior pituitary gland to regulate the secretion of adrenocorticotropic hormone (ACTH). ACTH, in turn, stimulates cortisol secretion from the zona fasciculata of the adrenal cortex. ACTH is also…

Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in the Fetus and Newborn Infant

Acknowledgments Research work in the senior author’s (TRK) laboratory is supported in part by the National Institutes of Health (AG056046, HD081162, AG029531, AG062319, HD097202) and The Makowski Family Endowment. Introduction The pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), influence the function of the differentiated gonad in utero and regulate gonadal function in later life. LH and FSH are glycoprotein hormones secreted by the same…

Growth Hormone, Prolactin, and Placental Lactogen in the Fetus and Newborn

Introduction and Background In the fully developed organism, growth hormone (GH), a 22-kDa molecule of 191 amino acids, is synthesized by acidophil cells in the anterior pituitary gland under the direction of hypothalamic GH-releasing hormone, which binds to its G protein–coupled receptor to stimulate GH secretion, and via somatotropin release–inhibiting factor, also known as somatostatin, an inhibitor of GH release in a “dominant negative” manner. The…

Growth Factor Regulation of Fetal Growth

Introduction Growth during fetal life is characterized by an early period of cell division and organogenesis, followed by a more prolonged period of growth and refinement of organ development. Growth factors are peptides or proteins that serve as key regulators of cell proliferation and differentiation that exert their effects by binding to specific receptors, which mediate signal transduction across cell membranes. This binding triggers a cascade…

Hypothalamus: Neuroendometabolic Center

Acknowledgment The editors wish to thank authors Adda Grimberg and Jessica Katz Kutikov for their excellent contribution to this text in the fifth edition. This chapter has been reproduced here in the sixth edition essentially unchanged. Introduction Enabled by its strategic anatomy, the hypothalamus uniquely serves the interface between the neural and endocrine systems. It is at the same time a part of the brain, an…

Ontogenesis of Striated Muscle

Introduction Embryology is the basis for understanding the intimate relation between structures in different organ systems, such as the nervous system and muscle, and is primordial for understanding pathogenesis in disorders of development that in the human may present as one of the congenital myopathies. Demonstration of a defective gene provides an etiology but does not define morphogenesis. The timing and sequence of striated muscle maturation…

The Growth Plate: Embryologic Origin, Structure, and Function

Acknowledgments Disclosures: The authors report no conflict of interest, financial or otherwise, concerning the material or methods used in this study or the findings specified in this paper. Funding: There were no sources of financial or material support for this report. Introduction Skeletal formation and growth occur as a process of sequential morphologic and biochemical events that take place during fetal development. During development, bone tissue…

Development of Olfaction and Taste in the Human Fetus and Neonate

Olfaction Perception of odorous molecules is the oldest special sense in both phylogeny and ontogeny. Olfaction is the earliest special sense in evolution; even polyps and jellyfishes, possessing only a loose neural net without a brain or even a ganglion, can perceive noxious odors and chemicals in their surrounding water and retract in response, or respond positively to attractants (i.e., food), noted as early as 1849…

Early Development of the Human Auditory System

Acknowledgments Preparation of this chapter was supported by grants from the National Institute on Deafness and Other Communication Disorders (R01DC011555 and R01DC017924 [DJT], F32DC018195 [KLA], and K23DC013583 [KMU]). Early Morphology and Physiology This section reviews the course of morphologic development of the auditory system and the physiologic correlates of these events in both humans and nonhumans. In studies of nonhumans, the function of the auditory system…

Neuroprotective Therapeutic Hypothermia

Acknowledgments Our work reported in this chapter is supported by the Health Research Council of New Zealand, the National Institutes of Health, the Lottery Health Board of New Zealand, the Auckland Medical Research Foundation, and the Neurological Foundation of New Zealand. Introduction Moderate to severe hypoxic-ischemic encephalopathy (HIE) continues to be a significant cause of acute neurologic injury at birth, occurring in approximately 1 to 2…

Cellular and Molecular Mechanisms of Neonatal Brain Injury and Neuroprotection

Acknowledgments We thank Drs. Billie Short, Nickie Andescavage, and Nneka Nzegwu (Division of Neonatology, Children’s National Hospital); Dr. Taeun Chang (Neonatal Neurology Program, Division of Epilepsy, Neurophysiology & Critical Care, Children’s National Hospital); and Dr. Hideo Jinno (Center for Neuroscience Research, Children’s National Hospital and Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences) for critically reading this chapter. The research program…

Pathophysiology of Neonatal White Matter Injury

White Matter Injury in the Preterm Neonate Preterm birth is a major public health issue affecting an estimated 13 million babies worldwide; one in eight deliveries in the United States are now preterm. Over the past two decades, improved neonatal intensive care unit (NICU) therapies have reduced the mortality and increased the survival of preterm newborns. Despite these advances in neonatal intensive care, preterm birth remains…

Intraventricular Hemorrhage in the Neonate

Introduction Germinal matrix hemorrhage–intraventricular hemorrhage (IVH) is the commonest form of intracranial hemorrhage in the newborn and is characteristic of the premature infant. The incidence of IVH in premature infants was documented to decline from very high rates of 34% to 49% in the 1970s to approximately 20% in the late 1980s. , There has also been a modest reduction in the rates of severe IVH…

Electroencephalography in the Preterm and Term Infant

Introduction Despite the evolution of new technologies for assessing neonatal brain function, electroencephalography (EEG) remains one of the most valuable diagnostic and prognostic tools. It is considered the gold standard for distinguishing epileptic seizures from nonepileptic paroxysmal events and for detecting subclinical seizure activity in high-risk babies. In babies who are severely ill, EEG is a more efficient predictive test than the neurologic examination. Background patterns,…

Cerebellar Development—The Impact of Preterm Birth and Comorbidities

Introduction It is well known that preterm birth is associated with increased risks of brain injury and impaired brain development resulting in impairments in motor, cognitive, and behavioral function. However, the focus has traditionally been on brain injury patterns in the cerebrum, such as intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). In recent years, it has become evident that the cerebellum is another major target for…

Developmental Aspects of Pain

Acknowledgments Ruth Grunau’s research is supported by the Canadian Institute of Health Research (CIHR) and a Senior Scientist salary award from the BC Children’s Hospital Research Institute. Simon Beggs’ research is supported by the Medical Research Council (MRC, UK) and National Institute of Academic Anaesthesia (NIAA). Introduction Pain is an intrinsic experience which is processed early in life by the maturing nervous system. However, for an…

Trophic Factor, Nutritional, and Hormonal Regulation of Brain Development

Introduction This chapter reviews advances in our understanding of the roles of neurotrophic proteins, retinoids, folate, lipids, and thyroid and steroid hormones in neural development. These molecules play central roles in the regulation of neuronal and glial lineages; when they are not maintained at optimal levels in the developing nervous system, neural structural abnormalities and permanent neurologic dysfunction may result. For example, maternal folate deficiency increases…

Development of the Blood-Brain Barrier

Acknowledgments Some of the work on which this chapter is based was supported by National Institutes of Health (NIH) grants R01-HD34618 and 1R01-HD-057100. Introduction The blood-brain barrier (BBB) is a selective diffusion barrier that maintains central nervous system (CNS) homeostasis and limits the entry of substances that could potentially alter neuronal function. The main anatomic substrate of the BBB is the specialized cerebral microvascular endothelium. It…

Mechanisms of Cell Death in the Developing Brain

Introduction When the brain is exposed to stress, a number of adaptive responses can act to reestablish homeostasis. However, when the stress is severe and/or the endogenous protective processes are not sufficiently effective, the cell will die. , Cell death can be initiated by numerous organelles (e.g., nucleus, mitochondrion, endoplasmic reticulum/lysosome, cytoskeleton, plasma membrane) and mitochondria, in particular, play a key role in the initiation and…

Development of the Nervous System

Introduction The human brain arises from a restricted population of embryonic cells to become the most complex organ system known during the brief 280 days of human gestation. The newborn brain is comprised of billions of neurons and glia arranged and interconnected in an exquisitely precise three-dimensional network. Unfortunately, minor changes have profound implications for postnatal development and function. Overlapping genetic and epigenetic events during neurodevelopment…