Gonzalez Pau, Burgaya Ferran, Acarin Laia, Peluffo Hugo, Castellano Bernardo, Gonzalez Berta
Medical Histology, Department of Cellular Biology, and Neuroscience Institute, Autonomous University of Barcelona, Barcelona, Spain.
J Neuropathol Exp Neurol. 2009 Apr;68(4):391-403. doi: 10.1097/NEN.0b013e31819dca30.
Inflammation is an important determinant of the severity and outcome of central nervous system injury. The endogenous anti-inflammatory cytokine interleukin-10 (IL-10) is upregulated in the injured adult central nervous system where it controls and terminates inflammatory processes. The developing brain, however, displays differences in susceptibility to insults and in associated inflammatory responses from the adult brain; the anatomic and temporal patterns of injury-induced IL-10 expression in the immature brain after excitotoxic injury are unknown. We analyzed the spaciotemporal gene and protein expression of IL-10 and its receptor (IL-10RI) in N-methyl-d-aspartate-induced excitotoxic injury in 9-day-old and control rats using quantitative reverse transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. In noninjected control brains, both molecules were expressed mainly in white matter on glial cells and blood vessels; IL-10 was also observed on blood vessels in gray matter and in glial fibrillary acidic protein-positive processes in the hippocampus and near leptomeningeal and ventricle surfaces. In N-methyl-d-aspartate-injected brains, IL-10 gene and protein expression were maximal at 72 hours postinjection; IL-10RI gene and protein expression peaked at 48 hours postinjection. Interleukin-10 and IL-10RI expression in injured areas was mainly found in reactive astrocytes and in microglia/macrophages. The expression patterns of IL-10 and IL-10R suggest possible developmental roles, and their upregulation after injury suggests that this expression may have anti-inflammatory effects in distinct anatomic sites in the immature brain.
炎症是中枢神经系统损伤严重程度和预后的重要决定因素。内源性抗炎细胞因子白细胞介素-10（IL-10）在成年中枢神经系统损伤时上调，在其中控制并终止炎症过程。然而，发育中的脑在对损伤的易感性以及相关炎症反应方面与成年脑存在差异；兴奋性毒性损伤后未成熟脑中损伤诱导的IL-10表达的解剖学和时间模式尚不清楚。我们使用定量逆转录聚合酶链反应、酶联免疫吸附测定和免疫组织化学分析了9日龄大鼠和对照大鼠在N-甲基-D-天冬氨酸诱导的兴奋性毒性损伤中IL-10及其受体（IL-10RI）的时空基因和蛋白表达。在未注射的对照脑中，这两种分子主要在胶质细胞和血管的白质中表达；在灰质血管以及海马、软脑膜和脑室表面附近的胶质纤维酸性蛋白阳性突起上也观察到了IL-10。在注射N-甲基-D-天冬氨酸的脑中，IL-10基因和蛋白表达在注射后72小时达到最大值；IL-10RI基因和蛋白表达在注射后48小时达到峰值。损伤区域的白细胞介素-10和IL-10RI表达主要见于反应性星形胶质细胞和小胶质细胞/巨噬细胞。IL-10和IL-10R的表达模式提示了可能的发育作用，其损伤后上调表明这种表达可能在未成熟脑的不同解剖部位具有抗炎作用。
