Fourth ventricle

The area postrema is a circumventricular brain region positioned on the dorsal surface of the medulla on the floor of the fourth ventricle. The blood-brain barrier and the cerebrospinal fluid-brain barrier are absent in this region and consequently many substances that do not pass across capillaries in other regions of the brain can do so in the area postrema. The chemoreceptor trigger zone (CTZ), located in the lateral area postrema is sensitive to blood-borne emetogens. Nerves from the CTZ connect with the vomiting centre. 

The locus ceruleus is a structure located on the floor of the fourth ventricle in the rostral pons. It contains more than 50% of all noradrenergic neurons in the brain, and projects to almost all areas of the central nervous system. 

Chemoreceptor trigger zone Located in the area postrema of the fourth ventricle of the brain, it is exposed to cerebrospinal fluid and blood and is easily stimulated by circulating toxins to induce nausea and vomiting. 

There are a few reports on possible sites of action of 5-HT3 antagonists. Low doses of zacopride administered directly into the fourth ventricle (i.c.v.) antagonized cisplatin (i.v.[-induced emesis in the cat [108]. A similar antagonism was demonstrated when routes of drug administration were interchanged. Similarly, GR 38032F, GR 65630 and MDL 72222, administered i.c.v. onto the area postrema at very low doses, antagonized cisplatin-induced... 

Now let us go back to methyldopa. The afore-mentioned experiments by HENNING and van ZWIETEN (21) indicated a central mode of action. HEISE and KRONEBERG (22), perfusing part of the third and the entire fourth ventricle of the brain in cats with methyldopa, a-me-thyldopamine and a-methylnoradrenaline were able to show a decrease in blood pressure. These effects were significantly blocked by pretreatment with yohimbine and to a lesser extent by phentolamine. These experiments support the concept of blood pressure lowering by an action on central a-adrenoreceptors. 

Cerebrospinal fluid is produced in chambers within the brain called ventricles. Two lateral ventricles and a midline third ventricle are contained within the cerebrum, while the fourth ventricle exists within the brain stem. CSF is produced by the choroid plexus in the lateral and third ventricles. It flows out through the ventricles by a series of aqueducts and into subarachnoid space. CSF supports the brain and spinal cord, ab-... 

The blood-brain barrier is not found in all parts of the brain. Certain small areas, including the area postrema beneath the floor of the fourth ventricle, an area in the preoptic recess, and portions of the floor of the third ventricle surrounding the stalk of the pituitary, appear to be devoid of this barrier. 

Detach the cerebellum and other neural tissue from the unsectioned portion of the head and examine the midbrain, cerebellum, medulla oblongata, cerebral aqueduct, and fourth ventricle. 

The three respective brain vesicles are discernible as they are demarcated by a small notch between the forebrain and midbrain (the forebrain-midbrain junction) and the midbrain and hindbrain (the isthmus) (Fig. 7 brackets). At this time, the fourth ventricle is also present and undergoing expansion over the hindbrain. 

Norepinephrine is widely distributed throughout brain in a nonuniform pattern, discrete from that of other amine systems such as dopamine and serotonin, although overlapping in several areas. The majority of noradrenergic axons and nerve endings found in the brain originate from the locus co-eruleus, a small, well-delineated cluster of cell bodies located in the pontine brain stem, just below the floor of the fourth ventricle. Given the wide distribution of norepinephrine in the brain [widely documented in the psychiatric literature), remarkably few neurons, estimated as 12,000 neurons on each... 

The adrenergic pathways that use epinephrine as a neurotransmitter, which have been explored only recently. One of these systems is also tegmental and is mixed with noradrenergic cells. The other is thalamic-hypothalamic, involved with the vagus nerve. Some adrenergic fibers are also found in the fourth ventricle and the spinal cord. 

The chemoreceptor trigger zone (CTZ) is iocated in the area postrema, ciose to the fourth ventricle, and is one of the four circumventricuiar organs which iie outside the biood-brain barrier. This allows the transfer of chemicals (endogenous and exogenous) directly into the CTZ from the cerebrospinal fluid (CSF). 

The "chemoreceptor trigger zone" or area postrema is located at the caudal end of the fourth ventricle. This is outside the blood-brain barrier but is accessible to emetogenic stimuli in the blood or cerebrospinal fluid. The chemoreceptor trigger zone is rich in dopamine D2 receptors and opioid receptors, and possibly serotonin5-HT3 receptors and NKi receptors. 

Martens, D.J., Seaberg, R.M., van der Kooy, D. (2002). In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord. Eur JNeurosci, 16, 1045-57. 

The cerebellum lies posterior to the brainstem and is separated from it by the fourth ventricle. Anatomically it is divided into two hemispheres, each consisting of three lobes (anterior, posterior, and flocculonodular). The function of the cerebellum is to help plan and coordinate motor activity and to assume responsibility for comparing the actual movement with the intended motor pattern. The cerebellum interprets various sensory input and helps modulate motor output so that the actual movement closely resembles the intended motor program. The cerebellum is also concerned with the vestibular mechanisms responsible for maintaining balance and posture. Therapeutic medications are not usually targeted directly for the cerebellum, but incoordination and other movement disorders may result if a drug exerts a toxic side effect on the cerebellum. 

The chemoreceptor trigger zone, which is a narrow strip along the floor of the fourth ventricle located close to the vomiting center... 

The respiration is at first accelerated. During the spasms, it is irregular. The volume then diminishes. It may assume the Cheyne-Stokes type. Respiratory paralysis is the usual cause of death. This is also the first center to fail when the cocaine is applied locally to the fourth ventricle. 

The result of this anatomical characteristic of endothelial cells in the CNS is an increased resistance to water-soluble and ionized drugs entering the brain, and cerebrospinal fluid (CSF), from capillary blood. However, in a few areas of the brain the barrier is absent. These areas include the lateral nuclei of the hypothalamus, the area postrema of the fourth ventricle, the pineal body, and the posterior lobe of the hypophysis. Highly lipophilic compounds can cross the barrier. Tranquilizers such as diazepam and its analogs are known to gain access rapidly to the CSF with a half-life (tm) entry time of less than 1 minute. 

The BBB is found throughout the brain and spinal cord except for a small number of isolated regions of brain that line the ventricles, the large cavities in the middle of the brain. These circumventricular organs (CVOs) include the choroid plexus (a patch of tissue that lines the floors of the ventricles and manufactures cerebrospinal fluid), the median eminence of the hypothalamus, the subfornical organ at the roof of the third ventricle and the area postrema at the base of the fourth ventricle. 

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