The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.
The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.
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DOI：
10.1007/s12028-021-01431-w
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发表时间：
2022-06
影响因子：
3.5
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中科院分区：
文献类型：
--
作者：
当患者在中风、创伤性脑损伤或心脏骤停后到达急诊科时，没有可用的治疗药物来帮助保护他们受危害的神经元。一个重要的原因是，我们还没有确定导致新损伤灰质电故障、神经元肿胀和血管收缩的分子机制。这三种现象都是由一种称为扩散去极化(SD)的过程产生的。由于我们对SD只有部分了解，我们缺乏分子靶点和生物标记物来帮助神经元在失去血流后存活，然后经历复发的SD。在这篇综述中，我们介绍SD是一种单一的或反复发生的事件，发生在失去血流后的灰质，这损害了Na+/K+泵。从每个SD事件中恢复电需要如此多的能量，以至于神经元通常在最初损伤后几分钟和几个小时内死亡，与细胞外谷氨酸无关。我们讨论了在众多的实验准备中，SD是如何被研究的各种陷阱，Na+/K+ATPase超负荷是如何引起SD的。升高的K+或谷氨酸不太可能是SD的自然激活剂。然后我们转向SD本身的性质，重点放在它的启动和传播以及计算机建模上。最后，我们总结了作者之间的共识和争论点，以及SD研究的可能方向。在随附的综述中，我们批评了谷氨酸兴奋毒性理论的作用，它如何塑造了SD研究，以及与SD理论相比，它对早期脑损伤研究的重要性值得怀疑。
When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.
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