Acarin L, González B, Castellano B
Unit of Histology, School of Medicine, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra 08193, Spain.
Eur J Neurosci. 2000 Oct;12(10):3505-20. doi: 10.1046/j.1460-9568.2000.00226.x.
Cytokines are important intercellular messengers involved in neuron-glia interactions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in postnatal day 9 rats, and the cytokines interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta 1 (TGF-beta1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL-6 and downregulation of TNFalpha and TGF-beta1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNFalpha and TGF-beta1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1beta and TNFalpha expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFalpha and IL-6, and microglia/macrophages showed mild IL-1beta and TGF-beta1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.
细胞因子是重要的细胞间信使，参与神经元与神经胶质细胞的相互作用以及小胶质细胞与星形胶质细胞的串扰，调节神经胶质细胞对脑损伤的反应和损伤结果。在本研究中，通过向出生后第9天的大鼠注射N-甲基-D-天冬氨酸诱导兴奋性毒性损伤，并通过酶联免疫吸附测定（ELISA）和/或免疫组织化学分析细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）和转化生长因子β1（TGF-β1）。此外，通过与胶质纤维酸性蛋白或番茄凝集素结合进行双重标记来鉴定表达细胞因子的神经胶质细胞。我们的结果表明，在兴奋性毒性损伤区域与未退化的周围灰质（SGM）中，神经元和神经胶质细胞均能够以不同模式表达细胞因子。兴奋性毒性损伤的神经元在退化前表现出IL-6上调以及TNFα和TGF-β1下调。此外，在SGM中，观察到神经元IL-6、TNFα和TGF-β1表达增加。位于SGM并显示IL-1β和TNFα表达的小胶质细胞亚群是注射后2-10小时最早产生细胞因子的神经胶质细胞。随后，在兴奋性毒性损伤区域和相邻白质中发现了细胞因子阳性神经胶质细胞：一些反应性星形胶质细胞表达TNFα和IL-6，小胶质细胞/巨噬细胞显示轻度IL-1β和TGF-β1。最后，在胶质瘢痕中观察到所有细胞因子的表达。如所讨论的，这种细胞因子产生模式表明它们参与了兴奋性毒性神经元损伤的演变及相关的神经胶质细胞反应。
