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      Substance P Regulation in Epilepsy

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          Abstract

          Background:

          Epilepsy is a common neurological disease characterized by abnormal temporary discharge of neurons in the central nervous system. In recent years, studies have revealed the localization and changes in the density of neuropeptides, such as substance P (SP) in the pathogenesis of epilepsy. This review is a concise overview of SP and their physiologic and pathologic functions on regulating epilepsy, and the underline mechanisms.

          Methods:

          We research and collect relative online content for reviewing the effects of SP in Epilepsy.

          Results:

          The SP/NK-1 receptor system may induce seizures and play an important role in status epilepticus and in experimental animal models of epilepsy. Newest studies show that several mechanisms may explain the excitatory effects of the SP/NK-1 receptor signaling pathway in epilepsy. By binding to the NK-1 receptor, NK-1 receptor antagonists may block the pathophysiological effects of SP, and further studies are needed to confirm the possible anti-epileptic activity of NK-1 receptor antagonists.

          Conclusion:

          SP plays crucial roles on through binding with NK-1 receptor during epilepsy pathologic processing, and the NK-1 receptor is receiving a great attention as a therapeutic target for treating epilepsy. Thus, the use of NK-1 receptor antagonists for the treatment of epilepsy should be investigated in further studies.

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          Most cited references104

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          The role of substance P in inflammatory disease.

          The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease. Copyright 2004 Wiley-Liss, Inc.
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            Adult epilepsy.

            The epilepsies are one of the most common serious brain disorders, can occur at all ages, and have many possible presentations and causes. Although incidence in childhood has fallen over the past three decades in developed countries, this reduction is matched by an increase in elderly people. Monogenic Mendelian epilepsies are rare. A clinical syndrome often has multiple possible genetic causes, and conversely, different mutations in one gene can lead to various epileptic syndromes. Most common epilepsies, however, are probably complex traits with environmental effects acting on inherited susceptibility, mediated by common variation in particular genes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations assist with diagnosis of the syndrome. Brain imaging is making great progress in identifying the structural and functional causes and consequences of the epilepsies. Current antiepileptic drugs suppress seizures without influencing the underlying tendency to generate seizures, and are effective in 60-70% of individuals. Pharmacogenetic studies hold the promise of being able to better individualise treatment for each patient, with maximum possibility of benefit and minimum risk of adverse effects. For people with refractory focal epilepsy, neurosurgical resection offers the possibility of a life-changing cure. Potential new treatments include precise prediction of seizures and focal therapy with drug delivery, neural stimulation, and biological grafts.
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              An unidentified depressor substance in certain tissue extracts.

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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                January 2018
                January 2018
                : 16
                : 1
                : 43-50
                Affiliations
                [1 ]The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun 130021, , Jilin , China;
                [2 ]China-Japan Union Hospital of Jilin University, Changchun 130031, , Jilin , China;
                [3 ]Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041 , PR China
                Author notes
                [* ]Address correspondence to these authors at the Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, PR China;, Tel: 0086-0431-88796386; E-mail: liguangquan@ 123456jlu.edu.cn (GQL) or, 11296986@ 123456qq.com (ZZ)
                [#]

                Guangfan Chi and Zhehao Huang contributed equally to this work.

                Article
                CN-16-43
                10.2174/1570159X15666170504122410
                5771382
                28474564
                4ed2b013-97c1-4178-aa91-6a2fb7e77cc0
                © 2018 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 24 March 2016
                : 18 June 2016
                : 27 April 2017
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                neuron,gaba,epilepsy,substance p,animal,nk-1
                Pharmacology & Pharmaceutical medicine
                neuron, gaba, epilepsy, substance p, animal, nk-1

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