Menyhárt Ákos, Zölei-Szénási Dániel, Puskás Tamás, Makra Péter, Bari Ferenc, Farkas Eszter
Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
Am J Physiol Heart Circ Physiol. 2017 Aug 1;313(2):H328-H337. doi: 10.1152/ajpheart.00222.2017. Epub 2017 Jun 9.
Spreading depolarization (SD) events contribute to lesion maturation in the acutely injured human brain. Neurodegeneration related to SD is thought to be caused by the insufficiency of the cerebral blood flow (CBF) response; yet the mediators of the CBF response, or their deficiency in the aged or ischemic cerebral cortex, remain the target of intensive research. Here, we postulated that tissue pH effectively modulates the magnitude of hyperemia in response to SD, the coupling of which is prone to be dysfunctional in the aged or ischemic cerebral cortex. To test this hypothesis, we conducted systematic correlation analysis between the direct current (DC) potential signature of SD, SD-associated tissue acidosis, and hyperemic element of the CBF response in the isoflurane-anesthetized, young or old, and intact or ischemic rat cerebral cortex. The data demonstrate that the amplitude of the SD-related DC potential shift, tissue acidosis, and hyperemia are tightly coupled in the young intact cortex; ischemia and old age uncouples the amplitude of hyperemia from the amplitude of the DC potential shift and acidosis; the duration of the DC potential shift, hyperemia and acidosis positively correlate under ischemia alone; and old age disproportionally elongates the duration of acidosis with respect to the DC potential shift and hyperemia under ischemia. The coincidence of the variables supports the view that local CBF regulation with SD must have an effective metabolic component, which becomes dysfunctional with age or under ischemia. Finally, the known age-related acceleration of ischemic neurodegeneration may be promoted by exaggerated tissue acidosis. The hyperemic element of the cerebral blood flow response to spreading depolarization is effectively modulated by tissue pH in the young intact rat cerebral cortex. This coupling becomes dysfunctional with age or under ischemia, and tissue acidosis lasts disproportionally longer in the aged cortex, making the tissue increasingly more vulnerable.
扩散性去极化（SD）事件促成急性损伤人脑的损伤成熟。与SD相关的神经退行性变被认为是由脑血流量（CBF）反应不足所致；然而，CBF反应的介质，或其在老年或缺血性大脑皮层中的缺乏，仍是深入研究的目标。在此，我们推测组织pH有效地调节了对SD反应的充血程度，而在老年或缺血性大脑皮层中，其耦合容易出现功能障碍。为验证这一假设，我们在异氟烷麻醉的年轻或老年、完整或缺血大鼠大脑皮层中，对SD的直流（DC）电位特征、与SD相关的组织酸中毒以及CBF反应的充血成分进行了系统的相关性分析。数据表明，在年轻完整皮层中，与SD相关的DC电位偏移幅度、组织酸中毒和充血紧密耦合；缺血和老龄使充血幅度与DC电位偏移幅度及酸中毒解耦；仅在缺血情况下，DC电位偏移、充血和酸中毒的持续时间呈正相关；在缺血情况下，老龄相对于DC电位偏移和充血不成比例地延长了酸中毒的持续时间。这些变量的一致性支持了这样一种观点，即SD介导的局部CBF调节必须有一个有效的代谢成分，而该成分在衰老或缺血时会出现功能障碍。最后，已知的与年龄相关的缺血性神经退行性变加速可能是由过度的组织酸中毒所促进。在年轻完整的大鼠大脑皮层中，组织pH有效地调节了对扩散性去极化的脑血流反应的充血成分。这种耦合在衰老或缺血时出现功能障碍，且老龄皮层中组织酸中毒持续时间不成比例地更长，使组织越来越脆弱。
