Ismail Fatme Seval, Corvace Franco, Faustmann Pedro M, Faustmann Timo Jendrik
Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany.
Front Cell Neurosci. 2021 Dec 16;15:805755. doi: 10.3389/fncel.2021.805755. eCollection 2021.
Astrocytes and microglia are the main cell population besides neurons in the central nervous system (CNS). Astrocytes support the neuronal network maintenance of transmitter and ion homeostasis. They are part of the tripartite synapse, composed of pre- and postsynaptic neurons and perisynaptic astrocytic processes as a functional unit. There is an increasing evidence that astroglia are involved in the pathophysiology of CNS disorders such as epilepsy, autoimmune CNS diseases or neuropsychiatric disorders, especially with regard to glia-mediated inflammation. In addition to astrocytes, investigations on microglial cells, the main immune cells of the CNS, offer a whole network approach leading to better understanding of non-neuronal cells and their pathological role in CNS diseases and treatment. An astrocyte-microglia co-culture model of inflammation was developed by Faustmann et al. (2003), which allows to study the endogenous inflammatory reaction and the cytokine expression under drugs in a differentiated manner. Commonly used antiepileptic drugs (e.g., levetiracetam, valproic acid, carbamazepine, phenytoin, and gabapentin), immunomodulatory drugs (e.g., dexamethasone and interferon-beta), hormones and psychotropic drugs (e.g., venlafaxine) were already investigated, contributing to better understanding mechanisms of actions of CNS drugs and their pro- or anti-inflammatory properties concerning glial cells. Furthermore, the effects of drugs on glial cell viability, proliferation and astrocytic network were demonstrated. The astrocyte-microglia co-culture model of inflammation proved to be suitable as unique model for pharmacological investigations on astrocytes and microglia with future potential (e.g., cancer drugs, antidementia drugs, and toxicologic studies).
星形胶质细胞和小胶质细胞是中枢神经系统（CNS）中除神经元外的主要细胞群体。星形胶质细胞支持神经元网络维持递质和离子稳态。它们是三联突触的一部分，三联突触由突触前和突触后神经元以及突触周围星形胶质细胞的突起组成，作为一个功能单元。越来越多的证据表明，星形胶质细胞参与中枢神经系统疾病如癫痫、自身免疫性中枢神经系统疾病或神经精神疾病的病理生理过程，特别是在胶质细胞介导的炎症方面。除了星形胶质细胞，对中枢神经系统主要免疫细胞小胶质细胞的研究提供了一种整体网络方法，有助于更好地理解非神经元细胞及其在中枢神经系统疾病和治疗中的病理作用。Faustmann等人（2003年）建立了一种炎症性星形胶质细胞-小胶质细胞共培养模型，该模型能够以分化的方式研究内源性炎症反应以及药物作用下的细胞因子表达。常用的抗癫痫药物（如左乙拉西坦、丙戊酸、卡马西平、苯妥英和加巴喷丁）、免疫调节药物（如地塞米松和干扰素-β）、激素和精神药物（如文拉法辛）已被研究，有助于更好地理解中枢神经系统药物的作用机制及其对胶质细胞的促炎或抗炎特性。此外，还证明了药物对胶质细胞活力、增殖和星形胶质细胞网络的影响。炎症性星形胶质细胞-小胶质细胞共培养模型被证明是一种适合对星形胶质细胞和小胶质细胞进行药理学研究的独特模型，具有未来潜力（如抗癌药物、抗痴呆药物和毒理学研究）。
