Erdener Şefik Evren, Dalkara Turgay
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Front Neurol. 2019 Aug 16;10:889. doi: 10.3389/fneur.2019.00889. eCollection 2019.
The cerebral microcirculation holds a critical position to match the high metabolic demand by neuronal activity. Functionally, microcirculation is virtually inseparable from other nervous system cells under both physiological and pathological conditions. For successful bench-to-bedside translation of neuroprotection research, the role of microcirculation in acute and chronic neurodegenerative disorders appears to be under-recognized, which may have contributed to clinical trial failures with some neuroprotectants. Increasing data over the last decade suggest that microcirculatory impairments such as endothelial or pericyte dysfunction, morphological irregularities in capillaries or frequent dynamic stalls in blood cell flux resulting in excessive heterogeneity in capillary transit may significantly compromise tissue oxygen availability. We now know that ischemia-induced persistent abnormalities in capillary flow negatively impact restoration of reperfusion after recanalization of occluded cerebral arteries. Similarly, microcirculatory impairments can accompany or even precede neural loss in animal models of several neurodegenerative disorders including Alzheimer's disease. Macrovessels are relatively easy to evaluate with radiological or experimental imaging methods but they cannot faithfully reflect the downstream microcirculatory disturbances, which may be quite heterogeneous across the tissue at microscopic scale and/or happen fast and transiently. The complexity and size of the elements of microcirculation, therefore, require utilization of cutting-edge imaging techniques with high spatiotemporal resolution as well as multidisciplinary team effort to disclose microvascular-neurodegenerative connection and to test treatment approaches to advance the field. Developments in two photon microscopy, ultrafast ultrasound, and optical coherence tomography provide valuable experimental tools to reveal those microscopic events with high resolution. Here, we review the up-to-date advances in understanding of the primary microcirculatory abnormalities that can result in neurodegenerative processes and the combined neurovascular protection approaches that can prevent acute as well as chronic neurodegeneration.
脑微循环对于满足神经元活动产生的高代谢需求至关重要。在功能上，无论在生理还是病理条件下，微循环实际上都与其他神经系统细胞密不可分。对于神经保护研究从实验室成功转化到临床应用而言，微循环在急性和慢性神经退行性疾病中的作用似乎未得到充分认识，这可能是一些神经保护剂临床试验失败的原因之一。过去十年越来越多的数据表明，诸如内皮细胞或周细胞功能障碍、毛细血管形态不规则或血细胞流动频繁动态停滞导致毛细血管通过时间过度不均一等微循环损伤，可能会显著损害组织的氧供应。我们现在知道，缺血诱导的毛细血管血流持续异常会对闭塞性脑动脉再通后的再灌注恢复产生负面影响。同样，在包括阿尔茨海默病在内的几种神经退行性疾病的动物模型中，微循环损伤可能伴随甚至先于神经细胞丢失出现。大血管相对容易通过放射学或实验成像方法进行评估，但它们无法如实反映下游的微循环紊乱，这种紊乱在微观尺度上可能在整个组织中差异很大，而且/或者发生得很快且短暂。因此，微循环组成部分的复杂性和规模需要利用具有高时空分辨率的前沿成像技术以及多学科团队的努力，以揭示微血管与神经退行性变之间的联系，并测试治疗方法以推动该领域的发展。双光子显微镜、超快超声和光学相干断层扫描技术的发展提供了有价值的实验工具，能够高分辨率地揭示这些微观事件。在此，我们综述了在理解可导致神经退行性变过程的原发性微循环异常以及可预防急性和慢性神经退行性变的联合神经血管保护方法方面的最新进展。
