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      The Neuroprotective Effect of Hericium erinaceus Extracts in Mouse Hippocampus after Pilocarpine-Induced Status Epilepticus

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          Abstract

          Hericium erinaceus (HE), a culinary-medicinal mushroom, has shown therapeutic potential in many brain diseases. However, the role of HE in status epilepticus (SE)-mediated neuronal death and its underlying mechanisms remain unclear. We investigated the neuroprotective effects of HE using a pilocarpine-induced SE model. Male C57BL/6 mice received crude extracts of HE (60 mg/kg, 120 mg/kg, or 300 mg/kg, p.o.) for 21 d from 14 d before SE to 6 d after SE. At 7 d after SE, cresyl violet and immunohistochemistry of neuronal nuclei revealed improved hippocampal neuronal survival in animals treated with 60 mg/kg and 120 mg/kg of HE, whereas those treated with 300 mg/kg of HE showed similar neuronal death to that of vehicle-treated controls. While seizure-induced reactive gliosis, assessed by immunohistochemistry, was not altered by HE, the number of hippocampal cyclooxygenase 2 (COX2)-expressing cells was significantly reduced by 60 and 120 mg/kg of HE. Triple immunohistochemistry demonstrated no overlap of COX2 labeling with Ox42, in addition to a decrease in COX2/GFAP-co-immunoreactivity in the group treated with 60 mg/kg HE, suggesting that the reduction of COX2 by HE promotes neuroprotection after SE. Our findings highlight the potential application of HE for preventing neuronal death after seizures.

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          Most cited references54

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          Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

          Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.
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            Epilepsy.

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              Epileptogenesis in the immature brain: emerging mechanisms.

              Epileptogenesis is defined as the process of developing epilepsy-a disorder characterized by recurrent seizures-following an initial insult. Seizure incidence during the human lifespan is at its highest in infancy and childhood. Animal models of epilepsy and human tissue studies suggest that epileptogenesis involves a cascade of molecular, cellular and neuronal network alterations. Within minutes to days following the initial insult, there are acute early changes in neuronal networks, which include rapid alterations to ion channel kinetics as a result of membrane depolarization, post-translational modifications to existing functional proteins, and activation of immediate early genes. Subacute changes occur over hours to weeks, and include transcriptional events, neuronal death and activation of inflammatory cascades. The chronic changes that follow over weeks to months include anatomical changes, such as neurogenesis, mossy fiber sprouting, network reorganization, and gliosis. These epileptogenic processes are developmentally regulated and might contribute to differences in epileptogenesis between adult and developing brains. Here we review the factors responsible for enhanced seizure susceptibility in the developing brain, and consider age-specific mechanisms of epileptogenesis. An understanding of these factors could yield potential therapeutic targets for the prevention of epileptogenesis and also provide biomarkers for identifying patients at risk of developing epilepsy or for monitoring disease progression.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                16 February 2019
                February 2019
                : 20
                : 4
                : 859
                Affiliations
                [1 ]Department of Physiology, Department of Biomedicine and Health Sciences, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; hjjang@ 123456catholic.ac.kr
                [2 ]Department of Pharmacology, Department of Biomedicine and Health Sciences, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; jonin12@ 123456naver.com (J.-E.K.); jeongkh81@ 123456yuhs.ac (K.H.J.); syk@ 123456catholic.ac.kr (S.Y.K.)
                [3 ]Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea
                [4 ]Department of Neurology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; sclim@ 123456catholic.ac.kr
                [5 ]Institute of Aging and Metabolic Diseases, The Catholic University of Korea, Seoul 06591, Korea
                Author notes
                [* ]Correspondence: kocho@ 123456catholic.ac.kr ; Tel.: +82-2-2258-7329; Fax: +82-2-536-2485
                [†]

                These authors equally contributed to this work.

                Author information
                https://orcid.org/0000-0002-1314-7584
                Article
                ijms-20-00859
                10.3390/ijms20040859
                6413080
                30781501
                b97bd335-f4b1-4f5e-9378-d51ad8fdf20f
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 January 2019
                : 14 February 2019
                Categories
                Article

                Molecular biology
                hericium erinaceus,status epilepticus,neuroprotection,anti-inflammation,cyclooxygenase 2,pilocarpine

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