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      Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders

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          Abstract

          Cell cultures are used in pharmaceutical, medical and biological sciences. Due to the ethical and cost limitations of in vivo models, the replaceable cell model that is more closely related to the characteristics of organisms, which has broad prospects and can be used for high-throughput drug screening is urgent. Neuronal and glial cell models have been widely used in the researches of neurological disorders. And the current researches on neuroinflammation contributes to blood-brain barrier (BBB) damage. In this review, we describe the features of healthy and inflamed BBB and summarize the main immortalized cell lines of the central nervous system (PC12, SH-SY5Y, BV2, HA, and HBMEC et al.) and their use in the anti-inflammatory potential of neurological disorders. Especially, different co-culture models of neuroinflammatory, in association with immune cells in both 2D and 3D models are discussed in this review. In summary, 2D co-culture is easily practicable and economical but cannot fully reproduce the microenvironment in vivo. While 3D models called organs-on-chips or biochips are the most recent and very promising approach, which made possible by bioengineering and biotechnological improvements and more accurately mimic the BBB microenvironment.

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          Neurotoxic reactive astrocytes are induced by activated microglia

          A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
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            The M1 and M2 paradigm of macrophage activation: time for reassessment

            Macrophages are endowed with a variety of receptors for lineage-determining growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial products. In tissues, macrophages mature and are activated in a dynamic response to combinations of these stimuli to acquire specialized functional phenotypes. As for the lymphocyte system, a dichotomy has been proposed for macrophage activation: classic vs. alternative, also M1 and M2, respectively. In view of recent research about macrophage functions and the increasing number of immune-relevant ligands, a revision of the model is needed. Here, we assess how cytokines and pathogen signals influence their functional phenotypes and the evidence for M1 and M2 functions and revisit a paradigm initially based on the role of a restricted set of selected ligands in the immune response.
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              Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.

              Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                23 April 2021
                2021
                : 12
                : 671734
                Affiliations
                [ 1 ]School of Pharmacy, Minzu University of China, Beijing, China
                [ 2 ]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [ 3 ]College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
                Author notes

                Edited by: Jian Gao, Second Affiliated Hospital of Dalian Medical University, China

                Reviewed by: Peng Cao, Nanjing University of Chinese Medicine, China

                Hua Wang, Anhui Medical University, China

                *Correspondence: Naihong Chen, Chennh@ 123456imm.ac.cn ; Zongran Pang, zrpang@ 123456163.com

                This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                671734
                10.3389/fphar.2021.671734
                8103160
                33967814
                aedbc0d9-2a5d-480c-a987-8a614d0011c9
                Copyright © 2021 Peng, Chu, Yang, Zhang, Pang and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 February 2021
                : 29 March 2021
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                neuroinflammation,blood brain barrier,glial cell,co-culture,neurological disorders

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