Monnet-Tschudi F, Zurich M-G, Honegger P
Department of Physiology, University of Lausanne, Lausanne, Switzerland.
Hum Exp Toxicol. 2007 Apr;26(4):339-46. doi: 10.1177/0960327107074589.
Brain inflammatory response is triggered by the activation of microglial cells and astrocytes in response to various types of CNS injury, including neurotoxic insults. Its outcome is determined by cellular interactions, inflammatory mediators, as well as trophic and/or cytotoxic signals, and depends on many additional factors such as the intensity and duration of the insult, the extent of both the primary neuronal damage and glial reactivity and the developmental stage of the brain. Depending on particular circumstances, the brain inflammatory response can promote neuroprotection, regeneration or neurodegeneration. Glial reactivity, regarded as the central phenomenon of brain inflammation, has also been used as an early marker of neurotoxicity. To study the mechanisms underlying the glial reactivity, serum-free aggregating brain cell cultures were used as an in vitro model to test the effects of conventional neurotoxicants such as organophosphate pesticides, heavy metals, excitotoxins and mycotoxins. This approach was found to be relevant and justified by the complex cell-cell interactions involved in the brain inflammatory response, the variability of the glial reactions and the multitude of mediators involved. All these variables need to be considered for the elucidation of the specific cellular and molecular reactions and their consequences caused by a given chemical insult.
脑炎性反应是由小胶质细胞和星形胶质细胞的激活所引发，以应对包括神经毒性损伤在内的各种类型的中枢神经系统损伤。其结果由细胞间相互作用、炎症介质以及营养和/或细胞毒性信号所决定，并取决于许多其他因素，如损伤的强度和持续时间、原发性神经元损伤和胶质细胞反应性的程度以及脑的发育阶段。根据具体情况，脑炎性反应可促进神经保护、再生或神经变性。胶质细胞反应性被视为脑炎症的核心现象，也被用作神经毒性的早期标志物。为了研究胶质细胞反应性的潜在机制，无血清聚集脑细胞培养物被用作体外模型，以测试有机磷农药、重金属、兴奋性毒素和霉菌毒素等传统神经毒物的作用。通过脑炎性反应中涉及的复杂细胞间相互作用、胶质细胞反应的变异性以及所涉及的多种介质，发现这种方法是相关且合理的。为了阐明特定化学损伤所引起的具体细胞和分子反应及其后果，所有这些变量都需要加以考虑。
