PDF(Pubmed)
Abstract：
Spreading depolarization (SD) is an electrochemical wave of neuronal depolarization mediated by extracellular K+ and glutamate, interacting with voltage-gated and ligand-gated ion channels. SD is increasingly recognized as a major cause of injury progression in stroke and brain trauma, where the mechanisms of SD-induced neuronal injury are intimately linked to energetic status and metabolic impairment. Here, I review the established working model of SD initiation and propagation. Then, I summarize the historical and recent evidence for the metabolic impact of SD, transitioning from a descriptive to a mechanistic working model of metabolic signaling and its potential to promote neuronal survival and resilience. I quantify the energetic cost of restoring ionic gradients eroded during SD, and the extent to which ion pumping impacts high-energy phosphate pools and the energy charge of affected tissue. I link energy deficits to adaptive increases in the utilization of glucose and O2, and the resulting accumulation of lactic acid and CO2 downstream of catabolic metabolic activity. Finally, I discuss the neuromodulatory and vasoactive paracrine signaling mediated by adenosine and acidosis, highlighting these metabolites\' potential to protect vulnerable tissue in the context of high-frequency SD clusters.
摘要：
扩散去极化(SD)是细胞外K+和谷氨酸介导的神经元去极化的电化学波,与电压门控和配体门控离子通道相互作用。SD越来越被认为是中风和脑外伤损伤进展的主要原因，其中SD诱导的神经元损伤的机制与能量状态和代谢障碍密切相关。这里,我回顾了已建立的SD启动和传播的工作模型。然后，我总结了SD代谢影响的历史和近期证据，从代谢信号的描述性工作模型过渡到机械工作模型及其促进神经元存活和复原力的潜力。我量化了恢复SD期间侵蚀的离子梯度的能量成本，以及离子泵送对高能磷酸盐池的影响程度和受影响组织的能量电荷。我将能量不足与葡萄糖和O2利用率的适应性增加联系起来，以及由此导致的乳酸和二氧化碳在分解代谢活动下游的积累。最后,我讨论了由腺苷和酸中毒介导的神经调节和血管活性旁分泌信号，突出这些代谢物在高频SD集群中保护脆弱组织的潜力。
