Remote limb ischemic postconditioning (RLIP) is a well-established neuroprotective strategy able to protect the brain from a previous harmful ischemic insult through a sub-lethal occlusion of the femoral artery. Neural and humoral mechanisms have been proposed as mediators required to transmit the peripheral signal from limb to brain. Moreover, different studies suggest that protection observed at brain level is associated to a general genetic reprogramming involving also microRNAs (miRNAs) intervention./nMethods: Brain ischemia was induced in male rats by transient occlusion of the middle cerebral artery (tMCAO), whereas RLIP was achieved by one cycle of temporary occlusion of the ipsilateral femoral artery after tMCAO. The expression profile of 810 miRNAs was evaluated in ischemic brain samples from rats subjected either to tMCAO or to RLIP. Among all analyzed miRNAs, there were four whose expression were upregulated after stroke and returned to basal level after RLIP, thus suggesting a possible involvement in RLIP-induced neuroprotection. These selected miRNAs were intracerebroventricularly infused in rats subjected to remote ischemic postconditioning, and their effect was evaluated in terms of brain damage, neurological deficit scores and expression of putative targets./nResults: Twenty-one miRNAs, whose expression was significantly affected by tMCAO and by tMCAO plus RLIP, were selected based on microarray microfluidic profiling. Our data showed that: (1) stroke induced an up-regulation of let-7a and miR-143 (2) these two miRNAs were involved in the protective effects induced by RLIP and (3) HIF1-α contributes to their protective effect. Indeed, their expression was reduced after RLIP and the exogenous intracerebroventricularly infusion of let-7a and miR-143 mimics prevented neuroprotection and HIF1-α overexpression induced by RLIP./nConclusions: Prevention of cerebral let-7a and miR-143 overexpression induced by brain ischemia emerges as new potential strategy in stroke intervention.

中文翻译：

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远程后处理可防止let-7a和miR-143上调，从而改善中风损害

远端肢体缺血后处理（RLIP）是一种行之有效的神经保护策略，能够通过股动脉亚致死性咬合保护大脑免受先前的有害缺血性损伤。已经提出了神经和体液机制作为将周围信号从四肢传递到大脑所需的介体。此外，不同的研究表明，在大脑水平观察到的保护与一般的基因重编程有关，其中还涉及microRNA（miRNA）的干预。雄性大鼠的大脑缺血是通过短暂闭塞大脑中动脉（tMCAO）引起的，而RLIP是通过在tMCAO之后暂时阻塞同侧股动脉一个周期来实现的。在接受tMCAO或RLIP的大鼠的缺血性脑样本中评估了810 miRNA的表达特征。在所有分析的miRNA中，有4个其中风后表达上调并在RLIP后恢复至基础水平，因此提示可能参与RLIP诱导的神经保护作用。这些选择的miRNA并入侧脑室中进行远程缺血后处理大鼠，并在脑损伤，神经功能缺损评分和推定targets./n的表达方面其效果进行了评价结果：基于微阵列微流分析技术，选择了21个表达受tMCAO和tMCAO加RLIP显着影响的miRNA。我们的数据表明：（1）中风诱导let-7a和miR-143上调（2）这两个miRNA参与了RLIP诱导的保护作用，（3）HIF1-α对其起保护作用。事实上，它们的表达RLIP和let-7a的外源性脑室内输注后减少的miR-143模拟物防止了神经保护和诱导RLIP./n HIF1-α的过表达结论：预防脑松懈7A和miR-143的过表达诱导的脑缺血已成为中风干预的新潜在策略。