Neuroanatomy, Hypothalamus (2023)

Introduction

Landmarks that define regions of the hypothalamus include the lamina terminalis, the pituitary gland, the mamillary bodies, and the superior hypothalamic sulcus.

The hypothalamus is a bilateral collection of nuclei divided into three zones around the third ventricle and the mamillary bodies. In general, the periventricular zone nuclei regulate the endocrine system, and the medial and lateral nuclei regulate autonomic and somatic behavior.

The hypothalamus is centrally located in the brain and connects to the brain stem via the dorsal longitudinal fasciculus, to the cerebral cortex via the medial forebrain bundle, to the hippocampus via the fornix, to the amygdala via the stria terminalis, to the thalamus via the mammillothalamic tract, the pituitary gland through the median. , and the retina via the retinohypothalamic tract.

structure and function

Generally speaking, the hypothalamus is a high-level sensory integration and motor output area that maintains homeostasis by controlling endocrine, autonomic, and somatic behavior.

First, the hypothalamus receives internal stimuli through receptors for circulating hormones. The blood-brain barrier is particularly permeable in the subfornical organ and in the organum vasculosum around the hypothalamus, allowing a sense of blood osmolarity. When osmolarity increases during dehydration, antidiuretic hormone (ADH) causes renal reabsorption of water. The hypothalamus senses external stimuli through the spinothalamic tract, which carries somatic sensory information, especially pain. The hypothalamus is involved in limbic sensory integration through the fornix and mammillothalamic tract of Papez's circuit and the connection of the stria terminalis to the amygdala. Sensory perceptions at the level of the cortex are received through the medial bundle of the forebrain. The retinohypothalamic tract carries light signals to the suprachiasmatic nucleus that regulate the daily pattern of hormone release. Integration of these inputs at the hypothalamic level leads to appropriate physiological and behavioral responses that sustain life over time.[1]

Second, hypothalamic output regulates the endocrine system, the autonomic system, and somatic behavior. There are 11 unique nuclei in the area below the thalamus.

The paraventricular and supraoptic nuclei produce the peptides oxytocin and ADH, which are released from neuronal axons in the posterior pituitary capillaries. These are hormones and neurotransmitters. Oxytocin in the systemic circulation controls the contraction of the uterus during labor and the milk that decreases during breastfeeding. Systemic ADH increases the translocation of aquaporin to the apical membrane of the distal convoluted tubule, increasing water absorption during dehydration. These hormones share a common peptide, which means that excess oxytocin, or the synthetic oxytocin used in labor and delivery, can activate renal ADH receptors. Thus, hyponatremia is a side effect of synthetic oxytocin. ADH also causes vasoconstriction to increase blood pressure in severe hypovolemia and releases von Willebrand factor from the Weibel-Palade bodies of endothelial cells to control bleeding. Furthermore, both oxytocin and ADH, which act as central neurotransmitters, are involved in pair binding.[2]

The preoptic, anterior, and posterior nuclei regulate body temperature by decreasing sympathetic tone to skeletal muscle, increasing sympathetic tone to the skin, dilating capillaries, and improving heat exchange with the outside. Males and females differ in the distribution of estrogen receptors in the preoptic nucleus, which affects sexual and maternal behavior.[3]

The suprachiasmatic nucleus regulates hormone secretion and daily behavior according to light entering through the eyes. The 24-hour oscillations of clock transcription factor activity and action potential frequency increase locomotor activity during the day and decrease at night—in addition, cortisol peaks around sunrise and growth hormone peaks around midnight. Most myocardial infarctions occur early in the morning due to the spike in cortisol, the stress hormone, which raises blood pressure.[4]

The ventromedial nucleus regulates feeding behavior. Destruction of this area causes hyperphagia, as seen in Prader-Willi syndrome. Satiety, perceived by this area, leads to a decrease in food intake. The dorsomedial nucleus controls anger behavior. Lack of satiety can lead to aggression. The lateral hypothalamus senses hunger and increases eating. Destruction of the lateral area causes anorexia.[5]

The arcuate nucleus releases hormones secreted by axon terminals in the hypothalamic-hypophyseal portal venous system to control the release of hormones from the anterior pituitary. Corticotropin-releasing hormone causes anterior pituitary cells to release adrenocorticotropic hormone (ACTH) into the capillaries that drain into the cerebral venous system. ACTH travels through the systemic circulation to stimulate the adrenal cortex (zona reticularis) to produce the stress response hormone cortisol. Due to its diversity of inputs, the hypothalamus allows the body to respond to physiological and psychological stressors. Again, cortisol production varies over the course of a 24-hour day, with the highest level at sunrise and the lowest at sunset due to the interconnections between the arcuate and suprachiasmatic nuclei. Thyrotropin-releasing hormone leads to the systemic secretion of TSH, which increases the synthesis and release of thyroid hormone to regulate metabolism. The hypothalamus senses the body's energy stores in part through receptors for the hormone leptin in adipocytes. When stores are low, the hypothalamus slows metabolism by reducing thyroid hormone.

Pulsed GnRH leads to increased release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Continuous GnRH causes decreased LH and FSH release. LH stimulates male testes to produce testosterone and female ovaries to produce estrogen. These hormones lead to secondary sexual development in males and females, respectively. An LH surge causes ovulation. FSH stimulates male spermatogenesis and female oocyte maturation. Growth hormone-releasing hormone (GHRH) leads to the release of growth hormone (GH), which stimulates tissue growth and metabolism. Somatostatin decreases GH release and antagonizes GHRH. Dopamine inhibits prolactin secretion as part of the hypothalamic-pituitary dopamine circuit. Phenothiazine antipsychotics interrupt this pathway, leading to a side effect of galactorrhea. Many of these hormones can be manipulated clinically by synthetic analogues. They are treatments for diseases such as uterine leiomyomas, anovulation, hypogonadism, breast and prostate cancer, contraceptives and acromegaly.[6]

The mammillary nucleus contributes to the limbic system as part of Papez's circuit. It is also involved in memory formation and controls exploratory behavior.[7]Bilateral mamillary body lesions are characteristic of Wernicke-Korsakoff syndrome, which presents with anterograde and possibly retrograde amnesia.

The hypothalamus sits at the top of a motor hierarchy, which includes the cerebral cortex, limbic system, brainstem, and spinal cord motor neurons. The hypothalamus integrates internal and external information about the state of the organism and controls patterns of action to maintain homeostasis throughout life. Sensory areas in the cerebral cortex provide abstract sensory perceptions. The limbic system provides powerful emotional stimuli. The spinohypothalamic tract provides information about pain and temperature. The brainstem produces serotonin and norepinephrine. The hypothalamus integrates these stimuli and activates action patterns and postures in the cerebral cortex and brainstem. These signals travel down the spine to the muscles and produce the behavior.[8]

Embryology

The notochord induces neurulation around the third week of gestation. Noggin, cordin, bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 8 (FGF8)are some of the genes involved. The neural tube forms from the ectoderm and closes by the sixth week. The rostral end will be the terminal lamina. The neural tube differentiates into three primary vesicles for the forebrain, midbrain, and hindbrain, in addition to the spinal cord. The forebrain differentiates into the telencephalon and diencephalon, the midbrain remains the midbrain, and the hindbrain becomes the metencephalon and myelencephalon. These structures continue to differentiate into adult brain structures. The hypothalamus and pituitary are derived from the diencephalon. In addition, the neural tube is separated into alar (sensory) and basal (motor) plates, which are separated by the sulcus limitans. The hypothalamus is derived from interneurons in the alarm plate, making it a sensory and motor integration center.[2]

Blood supply and lymphatic diseases

The hypothalamus is supplied by the circle of Willis, which surrounds the inferior, anteromedial branches of the anterior cerebral artery, the posteromedial branches of the posterior communicating artery, and the thalamoperforating branches of the posterior cerebral artery.

Venous drainage is largely through the circle of the intercavernous sinuses. The hypothalamic-neurohypophyseal portal system is a capillary plexus that transmits hormone-releasing hormones from the arcuate nucleus of the hypothalamus to the anterior pituitary gland.

Astroglial podocytes form the blood-brain barrier surrounding podocytes around capillaries. These cells protect the brain from toxins in the blood and facilitate the transport of nutrients to neurons. Astroglia also form a system of microscopic perivascular channels that permeate the brain and transmit lymphatics similar to cerebrospinal fluid (CSF). The system allows the CSF to remove metabolic waste and distribute glucose, amino acids, lipids and neurotransmitters. This system is most active during sleep and contributes to your recovery function. Arterial pulsatility drives glymphatic flow, suggesting that exercise may also improve it. Aging, brain trauma, and ischemia reduce CSF flow. In addition, larger lymphatic vessels in the meninges help absorb interstitial fluid in the dural venous sinuses.[9][10]

surgical considerations

Pituitary adenomas are the most common tumors affecting the hypothalamus. They can exert a mass effect causing headache and visual changes, such as bitemporal hemianopia due to compression of the optic chiasm. They can produce hormones, causing endocrine disorders. Prolactinomas cause galactorrhea and suppress gonadotropins, leading to decreased libido and infertility. Growth hormone-producing tumors cause gigantism and acromegaly. ACTH-producing tumors cause Cushing's disease due to hypercortisolism. Tumors producing gonadotropins can cause precocious puberty or hirsutism. The preferred method of tumor removal is transsphenoidal. One complication is damage to the hypothalamus, which can cause osmotic, autonomic, or alimentary dysregulation.[11]Complications of surgery include SIADH, central diabetes insipidus, and cerebral salt wasting.

clinical significance

The hypothalamus regulates feeding through the leptin and ghrelin pathways. Energy expenditure is regulated through the balance between proopiomelanocortin (POMC)/cocaine and amphetamine-regulated transcription (CART) and neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the arcuate nucleus. Leptin is a hormone produced by adipocytes in relation to their energy reserves. High reserves mean high leptin. The arcuate nucleus of the hypothalamus receives the signal and decreases eating and increases energy expenditure through POMC/CART activity. These transmitters act in the nuclei responsible for feeding, increasing body temperature, metabolism, locomotor activity and the production of gonadotropins. On the contrary, the decrease in fat reserves leads to an increase in feeding and cortisol (through the action of NPY/AgRP transmitters in the hypothalamus) and a decrease in body temperature, metabolism, locomotion and the production of gonadotropins. There is ongoing investigation into the role of the MC4 receptor and leptin resistance in obesity.[12]

The hypothalamus is also responsible for the acute phase immune response. White blood cells cause endothelial production of PGE2, which activates prostaglandin receptors in the paraventricular and preoptic nuclei. This causes fever by raising the body temperature set point, triggering a sympathetic response and causing muscle contractions (chills). Hepatic production of cortisol and acute phase proteins is increased. These effects accumulate in the malaise and unhealthy behavior typical of many illnesses.[13]

• Prolactin leads to lymphocyte survival and induces differentiation of oligodendrocyte precursors. Multiple sclerosis usually improves during pregnancy.[14]

• The mammillary bodies are destroyed by thiamine deficiency, leading to Wernicke's encephalopathy and Korsakoff's psychosis with prominent amnesia.[15]

• Cerebral salt loss is a common complication of traumatic brain injury, stroke, or intracranial hemorrhage. Findings include hypotonic hyponatremia and polyuria with increased urinary sodium. Treatment is salt supplementation followed by fludrocortisone.

• SIADH is a complication of hypothalamic damage or neurosurgery or AIDS. Findings include hypotonic hyponatremia, oliguria with increased sodium in the urine. Treatment is water restriction followed by hypertonic saline and then demeclocycline.

• Central diabetes insipidus caused by hypothalamic damage, decreasing ADH production. Findings include polyuria without concentration. The treatment is desmopressin.

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