The ischemic tolerance (IT) paradigm represents a fundamental cell response to certain types or injury able to render an organ more "tolerant" to a subsequent, stronger, insult. During the 16th century, the toxicologist Paracelsus described for the first time the possibility that a noxious event might determine a state of tolerance. This finding was summarized in one of his most important mentions: "The dose makes the poison". In more recent years, ischemic tolerance in the brain was first described in 1991, when it was demonstrated by Kirino and collaborators that two minutes of subthreshold brain ischemia in gerbils produced tolerance against global brain ischemia. Based on the time in which the conditioning stimulus is applied, it is possible to define preconditioning, perconditioning and postconditioning, when the subthreshold insult is applied before, during or after the ischemic event, respectively. Furthermore, depending on the temporal delay from the ischemic event, two different modalities are distinguished: rapid or delayed preconditioning and postconditioning. Finally, the circumstance in which the conditioning stimulus is applied on an organ distant from the brain is referred as remote conditioning. Over the years the "conditioning" paradigm has been applied to several brain disorders and a number of molecular mechanisms taking part to these protective processes have been described. The mechanisms are usually classified in three distinct categories identified as triggers, mediators and effectors. As concerns the putative effectors, it has been hypothesized that brain cells appear to have the ability to adapt to hypoxia by reducing their energy demand through modulation of ion channels and transporters, which delays anoxic depolarization. The purpose of the present review is to summarize the role played by plasmamembrane proteins able to control ionic homeostasis in mediating protection elicited by brain conditioning, particular attention will be deserved to the role played by Na+/Ca2+ exchanger.

中文翻译：

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钠/钙交换剂是缺血耐受引起的内源性神经保护的主要效应物。

缺血耐受（IT）范例代表了对某些类型或损伤的基本细胞反应，能够使器官对随后的更强的损伤更具“耐受性”。在16世纪，毒物学家Paracelsus首次描述了有害事件可能决定耐受状态的可能性。在他最重要的提及之一中总结了这一发现：“剂量使毒药产生”。近年来，大脑的局部缺血耐受始于1991年，当时Kirino及其合作者证明，沙鼠的2分钟亚阈下脑缺血产生了对整体脑局部缺血的耐受性。根据施加条件刺激的时间，可以定义预处理，过调节和后调节，当分别在缺血事件之前，之中或之后施加亚阈值侮辱。此外，根据缺血事件的时间延迟，可以区分两种不同的方式：快速或延迟预处理和后处理。最后，将调节刺激施加在远离大脑的器官上的情况称为远程调节。多年来，“调节”范式已应用于几种脑部疾病，并且已经描述了参与这些保护过程的许多分子机制。这些机制通常分为三个不同的类别，分别是触发器，介体和效应器。关于假定的效应子，据推测，脑细胞似乎具有通过调节离子通道和转运蛋白来减少其能量需求而适应缺氧的能力，从而延迟了缺氧性去极化。本综述的目的是总结能够控制离子稳态的质膜蛋白在介导脑调节引起的介导保护中的作用，尤其应特别注意Na + / Ca2 +交换剂的作用。