Deng Mingyang, Xiao Han, Zhang Hainan, Peng Hongling, Yuan Huan, Xu Yunxiao, Zhang Guangsen, Hu Zhiping
Department of Hematology, The Second Xiangya Hospital, Central South UniversityChangsha, China.
Department of Neurology, The Second Xiangya Hospital, Central South UniversityChangsha, China.
Front Cell Neurosci. 2017 Jul 17;11:205. doi: 10.3389/fncel.2017.00205. eCollection 2017.
Recent studies have found that administration of stem cells or extracellular vehicles (EVs) derived from stem cells exert neuroprotective effects after transient global ischemia. However, the underlying mechanisms of this effect remain unclear, especially at the level of synaptic functions. In this study, we compared the suppressive effects on cyclooxygenase-2 (COX-2) upregulation by EVs derived from bone marrow mesenchymal stem cells (BMSC-EV), adipose tissue MSC (AdMSC-EV) and serum (serum-EV). Then we examined whether BMSC-EVs could restore functional integrity of synaptic transmission and plasticity. Mice were randomly assigned to four groups: sham, sham with EV treatment, ischemia and ischemia with EV treatment. EVs were administered by intracerebroventricular injection (ICVI). We examined the consequence of transient global ischemia on pre- and post-synaptic functions of the hippocampal CA3-CA1 synapses at basal level, and long-term potentiation (LTP), an activity-dependent form of synaptic plasticity. Then we tested the therapeutic effects of EVs on these synaptic deficits. Meanwhile, Morris water maze (MWM) test was performed to examine the efficacy of EVs in rescuing ischemia-induced impairments in spatial learning and memory. EV treatment significantly restored impaired basal synaptic transmission and synaptic plasticity, and improved spatial learning and memory compared with the control group. In addition, EVs significantly inhibited ischemia-induced pathogenic expression of COX-2 in the hippocampus. EVs exert ameliorating effects on synaptic functions against transient global cerebral ischemia, which may be partly attributed to suppression of COX-2 pathogenic expression.
最近的研究发现，给予干细胞或源自干细胞的细胞外囊泡（EVs）在短暂性全脑缺血后具有神经保护作用。然而，这种作用的潜在机制仍不清楚，尤其是在突触功能层面。在本研究中，我们比较了骨髓间充质干细胞来源的EVs（BMSC-EV）、脂肪组织间充质干细胞来源的EVs（AdMSC-EV）和血清来源的EVs（血清-EV）对环氧合酶-2（COX-2）上调的抑制作用。然后我们研究了BMSC-EVs是否能恢复突触传递和可塑性的功能完整性。将小鼠随机分为四组：假手术组、假手术+EV治疗组、缺血组和缺血+EV治疗组。通过脑室内注射（ICVI）给予EVs。我们在基础水平上检查了短暂性全脑缺血对海马CA3-CA1突触的突触前和突触后功能以及长时程增强（LTP，一种依赖活动的突触可塑性形式）的影响。然后我们测试了EVs对这些突触缺陷的治疗效果。同时，进行莫里斯水迷宫（MWM）测试以检查EVs在挽救缺血诱导的空间学习和记忆损伤方面的效果。与对照组相比，EV治疗显著恢复了受损的基础突触传递和突触可塑性，并改善了空间学习和记忆。此外，EVs显著抑制了缺血诱导的海马中COX-2的病理性表达。EVs对短暂性全脑缺血的突触功能具有改善作用，这可能部分归因于对COX-2病理性表达的抑制。
