Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain
Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain
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DOI：
10.1046/j.1460-9568.2000.00226.x
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发表时间：
2000-10-01
影响因子：
3.4
通讯作者：
Castellano, B
中科院分区：
文献类型：
--
作者：
Acarin, L;González, B;Castellano, B
细胞因子是参与神经元-胶质细胞相互作用和小胶质细胞-星形胶质细胞串扰的重要细胞间信使，调节神经胶质细胞对脑损伤的反应和损伤转归。本研究通过注射N-甲基-D-天冬氨酸建立新生大鼠兴奋性损伤模型，并用酶联免疫吸附试验和/或免疫组织化学方法检测细胞因子IL-1β、IL-6、肿瘤坏死因子-α和转化生长因子-β1的表达。此外，用胶质纤维酸性蛋白或番茄凝集素结合的双重标记方法鉴定了表达细胞因子的胶质细胞。我们的结果表明，神经元和神经胶质细胞在兴奋性毒性损伤区和非变性周围灰质(SGM)都有不同的细胞因子表达模式。兴奋性损伤神经元在变性前表现为IL-6表达上调，而肿瘤坏死因子α和转化生长因子-β1表达下调。此外，在SGM中，神经元IL-6、肿瘤坏死因子α和转化生长因子-β1的表达增加。在注射后2~10h，小胶质细胞亚群位于SGM内，表达IL-1β和TNFα，是最早产生细胞因子的胶质细胞。随后，在兴奋性损伤区域及邻近白质内可见细胞因子阳性的胶质细胞：部分反应性星形胶质细胞表达肿瘤坏死因子α和IL-6，小胶质细胞/巨噬细胞表达轻度的IL-1β和转化生长因子-β1。正如所讨论的，这种细胞因子的产生模式暗示了它们在兴奋性毒性神经元损伤和相关的神经胶质反应的进化中的意义。
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-1 beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF-beta 1) 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 TNF alpha and TGF-beta 1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNF alpha and TGF-beta 1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1 beta and TNF alpha 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 TNF alpha and IL-6, and microglia/macrophages showed mild IL-1 beta and TGF-beta 1. 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.