The Area Postrema and Vomiting

Miller, Alan D.; Leslie, R.A.

doi:10.1006/frne.1994.1012

Cited by 300 publications

(164 citation statements)

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“…Brainstem SP has been implicated in autonomic control [16,29] and in control of emetic reflexes [41,46,48]. Of greatest relevance to the current use of C. parva as a small-animal emesis model, SP was found in the brainstem areas held to be key mediators of the emetic reflex: The area postrema, solitary tract and nucleus, and dorsal motor nucleus of the vagus nerve [4,[24][25][26]31]. Interestingly, preliminary results using c-fos immunohistochemistry as a marker for neuronal activation suggest that following the delayedphase emetic response, fos is increased most strongly in areas associated with dense SPL-IR fiber plexi (Ray, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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Chemotherapy is an effective treatment but difficult to tolerate due to side effects like vomiting. Studies on the etiology of chemotherapy-related emesis have implicated brainstem nuclei and the neurotransmitter Substance P, among other substrates. Since rodents do not vomit, other species have been necessary as alternative models of chemotherapy-induced emesis. Of these, the least shrew (Cryptotis parva) has proven valuable due to its small size, hardiness, and close phylogenetic relationship with primates. However, very little neuroanatomical data on C. parva exist. We used histological and immunohistochemical techniques to provide neuroanatomical data to help validate C. parva as a model organism, especially for emesis research. Brains were sectioned and stained for Nissl substance or myelin, or immunofluorescently labeled for Substance P. Sections were photographed, traced, and reconstructed with standardized zero points, and these data used to create a stereotaxic atlas. The brain of C. parva was similar to but smaller than other mammalian brains, with the cerebellum and hippocampus demonstrating the biggest differences. Differences appeared to be related to the small size of the brain and the metabolic compromises required of such a small mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped, and correlated very well with SPL-IR observed in other species. Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus. These data demonstrate that the anatomical differences between C. parva and other mammals will not preclude its use as a model organism.

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Section: Discussionmentioning

confidence: 99%

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Ray

Darmani

2007

Brain Research

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“…18 In this study, samples were collected in standardized bottles with preservative, protected from ultraviolet light, and refrigerated to help stabilize the dopamine compound, and we did see a significant reduction in dopamine excretion with carbidopa. We could not measure the concentration of dopamine in the area postrema, a known vomiting center, 7 but we did find a significant correlation between free dopamine in the urine and symptom severity (figure 1). Finally, because FD is a very rare disorder, our study includes a small number of patients.…”

Section: Resultsmentioning

confidence: 81%

Hyperdopaminergic crises in familial dysautonomia

et al. 2013

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Objective: The purpose of this study was to determine whether carbidopa (Lodosyn), an inhibitor of dopa-decarboxylase that blocks the synthesis of dopamine outside the brain, is an effective antiemetic in patients with familial dysautonomia (FD) and hyperdopaminergic nausea/retching/vomiting attacks. Methods:We enrolled 12 patients with FD in an open-label titration and treatment study to assess the safety of carbidopa. We then conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate its antiemetic efficacy.Results: Previous fundoplication surgery in each patient studied prevented vomiting, but all of the subjects experienced severe cyclical nausea and uncontrollable retching that was refractory to standard treatments. Carbidopa at an average daily dose of 480 mg (range 325-600 mg/day) was well tolerated. In the double-blind phase, patients experienced significantly less nausea and retching while on carbidopa than on placebo ( p , 0.03 and p , 0.02, respectively). Twenty-fourhour urinary dopamine excretion was significantly lower while on carbidopa (147 6 32 mg/gCr) than while on placebo (222 6 41mg/gCr, p , 0.05).Conclusions: Carbidopa is a safe and effective antiemetic in patients with FD, likely by reducing the formation of dopamine outside the brain. Recurrent bouts of nausea, retching, and vomiting accompanied by tachycardia and hypertension following emotional or physiologic stresses are a common disabling feature of familial dysautonomia (FD) (Riley-Day syndrome or hereditary sensory and autonomic neuropathy type III).1,2 Standard antiemetics have little effectiveness during these episodes. Traditionally, patients with FD were advised to manage their episodes with benzodiazepines.3 Many quickly become tolerant and require increasing doses, which have been associated with respiratory depression. The central sympatholytic agent, clonidine, has been used with some success, but its use is limited by the unwanted side effects of sedation and hypotension.3 Metoclopramide has also been used, but it is frequently associated with tardive dyskinesia, and is therefore not suitable as a long-term therapy. 4 Newer agents like pregabalin are only moderately effective. 5Because of a developmental abnormality in the afferent neurons of the baroreflex, patients with FD are unable to restrain sympathetic outflow.6 Vomiting/retching attacks occur during sympathetic activation when dopamine spills over into the circulation. 2 We hypothesize, therefore, that vomiting is due to activation of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier. The purpose of this study was to determine whether carbidopa (Lodosyn, Merck & Co., Inc., Whitehouse Station, NJ), an inhibitor of dopa-decarboxylase that blocks the synthesis of dopamine outside the brain, 8 is an effective antiemetic in patients with FD. We present the results of a randomized, placebo-controlled trial conducted in patients with FD.

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“…2 The roles played by the AP in cardiovascular regulation, fluid balance, osmoregulation, and immunomodulation are more recent scientific findings. 4,5,17,23,24,28,30,34 Duvernoy and Risold published macroscopic images of The AP has the appearance of arched wings opened on either side of the floor of the fourth ventricle, facing the Magendie foramen and diverging from the central canal upward. The AP seems medially to cover the hypoglossal nucleus and the vagal trigone and laterally to extend far over the nucleus of the solitary tract.…”

Section: Discussionmentioning

confidence: 99%

The human area postrema: clear-cut silhouette and variations shown in vivo

Longatti

Porzionato²,

Basaldella

et al. 2015

JNS

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OBJECT The human area postrema (AP) is a circumventricular organ that has only been described in cadaveric specimens and animals. Because of its position in the calamus scriptorius and the absence of surface markers on the floor of the fourth ventricle, the AP cannot be clearly localized during surgical procedures. METHODS The authors intravenously administered 500 mg fluorescein sodium to 25 patients during neuroendoscopic procedures; in 12 of these patients they explored the fourth ventricle. A flexible endoscope equipped with dual observation modes for both white light and fluorescence was used. The intraoperative fluorescent images were reviewed and compared with anatomical specimens and 3D reconstructions. RESULTS Because the blood-brain barrier does not cover the AP, it was visualized in all cases after fluorescein sodium injection. The AP is seen as 2 coupled leaves on the floor of the fourth ventricle, diverging from the canalis centralis medullaris upward. Although the leaves normally appear short and thick, there can be different morphological patterns. Exploration using the endoscope's fluorescent mode allowed precise localization of the AP in all cases. CONCLUSIONS Fluorescence-enhanced inspection of the fourth ventricle accurately identifies the position of the AP, which is an important landmark during surgical procedures on the brainstem. A better understanding of the AP can also be valuable for neurologists, considering its functional role in the regulation of homeostasis, emesis, and cardiovascular and electrolyte balance. Despite the limited number of cases in this report, evidence indicates that the normal anatomical appearance of the AP is that of 2 short and thick leaves that are joined at the midline. However, there can be great variability in terms of the structure's shape and size.

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The Area Postrema and Vomiting

Cited by 300 publications

References 0 publications

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew (Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Hyperdopaminergic crises in familial dysautonomia

The human area postrema: clear-cut silhouette and variations shown in vivo

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