School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
Department of Anatomy and the Brain Health Research Center, Dunedin 9054, New Zealand; Centre for Translational Physiology, University of Otago Wellington, Dunedin 9054, New Zealand; Department of Psychology, University of Otago, Dunedin 9054, New Zealand.
Brain Behav Immun. 2015 Aug;48:57-67. doi: 10.1016/j.bbi.2015.02.014. Epub 2015 Mar 4.
Post-stroke patients describe suffering from persistent and unremitting levels of distress. Using an experimental model of focal cortical ischemia in adult male C57BL/6 mice, we examined whether exposure to chronic stress could modify the development of secondary thalamic neurodegeneration (STND), which is commonly reported to be associated with impaired functional recovery. We were particularly focused on the modulatory role of microglia-like cells, as several clinical studies have linked microglial activation to the development of STND. One month following the induction of cortical ischemia we identified that numbers of microglial-like cells, as well as putative markers of microglial structural reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and antigen presentation (MHC-II) were all significantly elevated in response to occlusion. We further identified that these changes co-occurred with a decrease in the numbers of mature neurons within the thalamus. Occluded animals that were also exposed to chronic stress exhibited significantly lower levels of Iba-1 positive cells and a reduced expression of Iba-1 and CD11b compared to the 'occlusion-alone' group. Interestingly, the dampened expression of microglial/monocyte markers observed in stressed animals was associated with significant additional loss of neurons. These findings indicate that the process of STND can be negatively modified, potentially in a microglial dependent manner, by exposure to chronic stress.
中风后患者常描述其处于持续性、无法缓解的痛苦之中。本研究采用成年雄性 C57BL/6 小鼠大脑皮质局灶性脑缺血的实验模型，探讨慢性应激是否会改变继发性丘脑神经退行性病变（STND）的发生，因为有研究报道 STND 与功能恢复受损有关。我们特别关注小胶质样细胞的调节作用，因为几项临床研究已将小胶质细胞激活与 STND 的发生联系起来。皮质缺血诱导一个月后，我们发现小胶质样细胞的数量以及小胶质细胞结构重排（Iba-1）、补体加工（CD11b）、吞噬作用（CD68）和抗原呈递（MHC-II）的假定标志物的数量均显著升高，这与闭塞反应有关。我们进一步发现，这些变化与丘脑内成熟神经元数量的减少同时发生。与“单纯闭塞”组相比，还暴露于慢性应激的闭塞动物的 Iba-1 阳性细胞数量明显减少，Iba-1 和 CD11b 的表达也降低。有趣的是，应激动物中小胶质细胞/单核细胞标志物表达的下调与神经元的显著额外丢失有关。这些发现表明，STND 过程可以通过慢性应激的暴露而受到负面影响，可能以小胶质细胞依赖的方式进行。
