Institute of Anatomy, Kiel University, 24118 Kiel, Germany.
Int J Mol Sci. 2024 Feb 8;25(4):2078. doi: 10.3390/ijms25042078.
Brain diseases are oftentimes life-threatening and difficult to treat. The local administration of drug substances using brain implants can increase on-site concentrations and decrease systemic side effects. However, the biocompatibility of potential brain implant materials needs to be evaluated carefully as implants can trigger foreign body reactions, particularly by increasing the microglia and astrocyte reactivity. To date, these tests have been frequently conducted in very simple in vitro models, in particular not respecting the key players in glial cell reactions and the challenges of surgical implantation characterized by the disruption of oxygen and nutrient supply. Thus, we established an in vitro model in which we treated human glial cell lines with reduced oxygen and glucose levels. The model displayed cytokine and reactive oxygen species release from reactive microglia and an increase in a marker of reactive astrocytes, galectin-3. Moreover, the treatment caused changes in the cell survival and triggered the production of hypoxia-inducible factor 1α. In this comprehensive platform, we demonstrated the protective effect of the natural polyphenol resveratrol as a model substance, which might be included in brain implants to ease the undesired glial cell response. Overall, a glial-cell-based in vitro model of the initial challenges of local brain disease treatment may prove useful for investigating new therapy options.
脑部疾病往往具有生命威胁且难以治疗。利用脑部植入物局部给药可以增加局部浓度并减少全身副作用。然而，潜在的脑部植入材料的生物相容性需要仔细评估，因为植入物会引发异物反应，特别是通过增加小胶质细胞和星形胶质细胞的反应性。迄今为止，这些测试经常在非常简单的体外模型中进行，特别是没有考虑到神经胶质细胞反应的关键参与者以及手术植入所带来的挑战，其中包括氧气和营养供应的中断。因此，我们建立了一个体外模型，用低氧和低糖水平处理人神经胶质细胞系。该模型显示了反应性小胶质细胞释放细胞因子和活性氧物质，并增加了反应性星形胶质细胞的标志物半乳糖凝集素-3。此外，这种处理导致细胞存活的变化，并触发缺氧诱导因子 1α 的产生。在这个综合平台上，我们证明了天然多酚白藜芦醇作为模型物质的保护作用，它可能被包含在脑部植入物中以减轻不期望的神经胶质细胞反应。总的来说，这种基于神经胶质细胞的体外模型可以模拟局部脑部疾病治疗的初始挑战，可能有助于研究新的治疗方法。
