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      Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma

      a , b , *

      Neuroendocrinology

      S. Karger AG

      Craniopharyngioma, Hypothalamus, Neurosurgery, Hypothalamic obesity

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          Abstract

          Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamus-sparing surgery. Also a postoperative hypothalamic damage evaluation with the use of hypothalamus volume measurement can predict hypothalamic obesity, which is important for early treatment options. The morbidity of CP includes cognitive dysfunction with attention deficits and impaired episodic memory and processing speed. Again patients with hypothalamic damage are more affected. Treatment options of hypothalamic obesity in the chronic phase are scarce and not convincingly successful. The most optimal situation is to try to hinder or stop the evolution of hypothalamic obesity. Prevention of hypothalamic damage is recommended, with special regard to hypothalamus-sparing therapeutic approaches that respect the integrity of essential nuclei located in both the medial and the posterior hypothalamic areas.

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          Most cited references 62

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          The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.

           A STUNKARD,  S Messick (1984)
          This report describes the construction of a questionnaire to measure three dimensions of human eating behavior. The first step was a collation of items from two existing questionnaires that measure the related concepts of 'restrained eating' and 'latent obesity', to which were added items newly written to elucidate these concepts. This version was administered to several populations selected to include persons who exhibited the spectrum from extreme dietary restraint to extreme lack of restraint. The resulting responses were factor analyzed and the resulting factor structure was used to revise the questionnaire. This process was then repeated: administration of the revised questionnaire to groups representing extremes of dietary restraint, factor analysis of the results and questionnaire revision. Three stable factors emerged: (1) 'cognitive restraint of eating', (2) 'disinhibition' and (3) 'hunger'. The new 51-item questionnaire measuring these factors is presented.
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            Interplay of hippocampus and prefrontal cortex in memory.

            Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss.

              Liraglutide is a glucagon-like peptide-1 (GLP-1) analog marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide also reduces body weight. It is not fully understood how liraglutide induces weight loss or to what degree liraglutide acts directly in the brain. Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus. Peripheral injection of fluorescently labeled liraglutide in mice revealed the presence of the drug in the circumventricular organs. Moreover, labeled liraglutide bound neurons within the arcuate nucleus (ARC) and other discrete sites in the hypothalamus. GLP-1R was necessary for liraglutide uptake in the brain, as liraglutide binding was not seen in Glp1r(-/-) mice. In the ARC, liraglutide was internalized in neurons expressing proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Electrophysiological measurements of murine brain slices revealed that GLP-1 directly stimulates POMC/CART neurons and indirectly inhibits neurotransmission in neurons expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP) via GABA-dependent signaling. Collectively, our findings indicate that the GLP-1R on POMC/CART-expressing ARC neurons likely mediates liraglutide-induced weight loss.
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                Author and article information

                Journal
                Neuroendocrinology
                Neuroendocrinology
                NEN
                Neuroendocrinology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                0028-3835
                1423-0194
                August 2020
                24 June 2020
                : 110
                : 9-10
                : 767-779
                Affiliations
                aDepartment of Endocrinology, Skåne University Hospital, Lund, Sweden
                bClinical Sciences, Lund University, Lund, Sweden
                Author notes
                *Eva-Marie Erfurth, Department of Endocrinology, Skåne University Hospital, Lasarettsgatan 15, SE–221 85 Lund (Sweden), Eva_Marie.Erfurth@ 123456med.lu.se
                Article
                nen-0110-0767
                10.1159/000509616
                7490511
                32580186
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                Page count
                Figures: 6, Tables: 2, References: 91, Pages: 13
                Categories
                At the Cutting Edge

                Endocrinology & Diabetes

                hypothalamic obesity, neurosurgery, hypothalamus, craniopharyngioma

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