Batlle Montserrat, Ferri Lorenzo, Andrade Carmen, Ortega Francisco-Javier, Vidal-Taboada Jose M, Pugliese Marco, Mahy Nicole, Rodríguez Manuel J
Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain ; Istituto di Anatomia Umana e Biologia Cellulare, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
Biomed Res Int. 2015;2015:102419. doi: 10.1155/2015/102419. Epub 2015 Apr 21.
Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.
脑损伤会引发一种由动态的星形胶质细胞-小胶质细胞相互作用所支持的进行性炎症反应。我们从海马兴奋性毒性损伤大鼠模型中神经元效应的角度，研究了星形胶质细胞-小胶质细胞相互作用的进行性慢性特征。注射N-甲基-D-天冬氨酸（NMDA）引发了一个在38天内具有萎缩、神经元丢失和星形胶质细胞介导的S100B快速增加特征的过程。小胶质细胞反应随损伤进展而变化。损伤后一天出现肿瘤坏死因子-α（TNF-α）分泌高峰，前三天内有短暂的YM1分泌。小胶质细胞糖皮质激素受体表达在第5天前增加，之后逐渐恢复到假手术组水平。为了进一步研究星形胶质细胞在小胶质细胞反应中的作用，我们用L-α-氨基己二酸与NMDA诱导的损伤同时进行短暂的星形胶质细胞消融。我们观察到神经元死亡显著持续，伴有小胶质细胞反应和增殖增强、YM1浓度增加、TNF-α分泌减少以及糖皮质激素受体表达降低。只有在星形胶质细胞恢复后，S100B反应性才增加。我们的结果表明存在一种初始的神经保护性小胶质细胞反应，星形胶质细胞可直接控制小胶质细胞的细胞毒性反应。我们提出恢复星形胶质细胞-小胶质细胞相互作用是组织的首要任务，以确保适当的细胞协调，从而限制脑损伤。
